Systems and methods for delivery of therapeutic gas

ABSTRACT

Therapy gas delivery systems that provide run-time-to-empty information to a user of the system and methods for administering therapeutic gas to a patient. The therapeutic gas delivery system may include a gas pressure sensor attachable to a therapeutic gas source that communicates therapeutic gas pressure data to a therapeutic gas delivery system controller, a gas temperature sensor positioned to measure gas temperature in the therapeutic gas source that communicates therapeutic gas temperature data to the therapeutic gas delivery system controller, at least one flow controller that communicates therapeutic gas flow rate data to the therapeutic gas delivery system controller, at least one flow sensor that communicates flow rate data to the therapeutic gas delivery system controller, and at least one display that communicates run-time-to-empty to a user of the therapeutic gas delivery system. The therapeutic gas delivery system controller of the system includes a processor that executes an algorithm to calculate the run-time-to-empty from the data received from the gas pressure sensor, temperature sensor, flow controller and flow sensor, and directs the result to the display.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.16/748,319, filed Jan. 21, 2020 which is a continuation of U.S.application Ser. No. 14/709,316, filed May 11, 2015 which claims thebenefit under 35 U.S.C. sctn.119(e) to U.S. Provisional Application No.61/991,028, filed May 9, 2014, U.S. Provisional Application No.61/991,032, filed May 9, 2014, and U.S. Provisional Application No.61/991,083, filed May 9, 2014, the entire contents of which areincorporated herein by reference in their entirety.

TECHNICAL FIELD

Systems and methods for managing delivery of a therapy gas from a gassource to a subject, and in particular to management of delivery ofinhaled therapy gases, are described.

BACKGROUND

Certain medical treatments include the use of therapy gases that areinhaled by the patient. Gas delivery systems are often utilized byhospitals to control the rate of therapy gas delivery to the patient inneed thereof, to verify the correct type of gas and the correctconcentration are being used. Gas delivery systems may also verifydosage information, patient information and therapy gas administration.

Known therapy gas delivery systems may include a computerized system fortracking patient information, including information regarding the typeof gas therapy, concentration of therapy gas to be administered anddosage information for a particular patient. While these computerizedsystems may communicate with other components of the therapy gasdelivery system, such as the valve on the gas source that controls theflow of gas to the computerized system and/or the ventilator foradministration to the patient, such communication has not included anability to determine the amount of treatment time left before thetherapy gas remaining in the gas source falls below a predeterminedminimum or the gas source is empty.

There is a need for a therapy gas delivery system that addresses atleast the above.

SUMMARY

Various embodiments are listed below. It will be understood that theembodiments listed below may be combined not only as listed, but inother suitable combinations in accordance with the spirit and scope ofthe invention.

A first embodiment relates to a therapeutic gas delivery system,comprising at least one gas supply subsystem comprising, a gas sourcecoupling configured to receive a therapeutic gas source and form a fluidflow connection with the therapeutic gas source, a gas source valveadjacent to and in fluid communication with the gas source coupling,wherein the gas source valve is configured to have at least an openstate and a closed state, a gas pressure sensor adjacent to and in fluidcommunication with the gas source valve, wherein the gas source valveprovides a gas flow path from the gas source coupling to the gaspressure sensor, and the gas pressure sensor is configured to measure agas pressure at the gas source coupling at least when the gas sourcevalve is in an open state, to be in communication over a communicationpath with a therapeutic gas delivery system controller comprising a CPU,and to communicate a pressure value over the communication path to thetherapeutic gas delivery system controller, and a therapeutic gas flowregulator down stream from the gas pressure sensor, gas source valve,and gas source coupling, and in fluid communication with the gas sourcecoupling, gas source valve, and gas pressure sensor, one or moredisplay(s) configured to be in communication over a communication pathwith the therapeutic gas delivery system controller, wherein the CPU ofthe therapeutic gas delivery system controller is configured tocalculate a value for a run-time-to-empty from a volume value, apressure value communicated from the gas pressure sensor, and an averagetherapeutic gas consumption rate calculated by the CPU from the gas flowrate value communicated from the therapeutic gas flow controller, andwherein the system display is configured to display the calculatedrun-time-to-empty value.

In a second embodiment, the therapeutic gas delivery system of the firstembodiment may be modified to further comprise a therapeutic gas sourcehaving a volume and containing a therapeutic gas at an initial pressurewithin the volume, wherein the therapeutic gas source is configured tobe operatively associated with the gas source coupling, and wherein thevolume value of the therapeutic gas source is inputted to thetherapeutic gas delivery system controller.

In a third embodiment, the therapeutic gas delivery system of the firstand/or second embodiments may be modified to have the gas supplysubsystem further comprise a therapeutic gas conduit having an interiorvolume that provides a gas flow path at least from the gas sourcecoupling to the gas source valve, and a temperature sensor operativelyassociated with the therapeutic gas source or the therapeutic gasconduit, wherein the temperature sensor is configured to measure atemperature of the therapeutic gas source, the therapeutic gas conduit,or the therapeutic gas, to be in communication over a communication pathwith a therapeutic gas delivery system controller, and to communicate atemperature value over the communication path to the therapeutic gasdelivery system controller.

In a fourth embodiment, the therapeutic gas delivery system of the firstthrough third embodiments may be modified to have the gas supplysubsystem further comprise a gas source identifier attached to thetherapeutic gas source, wherein the gas source identifier containsinformation at least of the gas source volume and the identity of thetherapeutic gas supplied by the therapeutic gas source, and a gas sourceidentifier reader operatively associated with the therapeutic gasdelivery system, and in communication over a communication path with thetherapeutic gas delivery system controller, wherein the gas sourceidentifier reader is configured to obtain identifying information fromthe gas source identifier when the therapeutic gas source is properlyreceived by the gas source coupling, and communicate the identifyinginformation to the therapeutic gas delivery system controller.

In a fifth embodiment, the therapeutic gas delivery system of the firstthrough fourth embodiments may be modified in a manner wherein thetherapeutic gas source is a compressed gas cylinder, and the gas sourceidentifier is selected from the group consisting of RFID, a QR code, abar code, or combinations thereof, which is affixed to an outer surfaceof the compressed gas cylinder.

In a sixth embodiment, the therapeutic gas delivery system of the firstthrough fifth embodiments may be modified in a manner wherein the gassupply subsystem further comprises a therapeutic gas source detectoroperatively associated with the gas source coupling, wherein thetherapeutic gas source detector is configured to detect when thetherapeutic gas source is properly received by the gas source coupling,and communicate a signal of the presence of the therapeutic gas sourceto the therapeutic gas delivery system controller.

In a seventh embodiment, the therapeutic gas delivery system of thefirst through sixth embodiments may be modified in a manner wherein thetherapeutic gas delivery system controller is configured to obtainidentifying information from the gas source identifier when thetherapeutic gas source detector detects the therapeutic gas source isproperly received by the gas source coupling, and communicate a signalto the gas source valve adjacent to the gas source coupling totransition to an open state, and wherein the therapeutic gas flowregulator is configured to be in communication over a communication pathwith the therapeutic gas delivery system controller.

In an eighth embodiment, the therapeutic gas delivery system of thefirst through seventh embodiments, may be modified in a manner whereinthe therapeutic gas delivery system controller is configured to obtain agas pressure value communicated from the gas pressure sensor, and a gasflow rate value from a flow controller, and calculate arun-time-to-empty value for the therapeutic gas source.

In a ninth embodiment, the therapeutic gas delivery system of the firstthrough eighth embodiments, may be modified in a manner wherein thetherapeutic gas delivery system controller is configured to calculatethe run-time-to-empty value for the therapeutic gas source from at leastthe gas pressure value, the temperature of the therapeutic gas source,the gas source volume, and an average therapeutic gas consumption rate.

In a tenth embodiment, the therapeutic gas delivery system of the firstthrough ninth embodiments, may be modified in a manner wherein thetherapeutic gas delivery system controller comprises hardware, software,firmware, or a combination thereof configured to perform arun-time-to-empty calculation.

In an eleventh embodiment, the therapeutic gas delivery system of thefirst through tenth embodiments, may be modified in a manner wherein atleast one of the one or more display(s) is a status display that isconfigured to present at least the run-time-to-empty value.

In a twelfth embodiment, the therapeutic gas delivery system of thefirst through eleventh embodiments, may be modified in a manner whereinat least one of the one or more display(s) is a status displayoperatively associated with at least one gas supply subsystem that isconfigured to present a bar graph, a chart, a numerical display of avalue, a visual alarm, identifying information from the gas sourceidentifier, or a combination thereof.

In a thirteenth embodiment, the therapeutic gas delivery system of thefirst through twelfth embodiments, may be modified in a manner whereinat least one status display operatively associated with at least one gassupply subsystem is configured to provide a user interface that isconfigured to provide control of the therapeutic gas delivery system.

In a fourteenth embodiment, the therapeutic gas delivery system of thefirst through thirteenth embodiments, may be modified in a mannerwherein the therapeutic gas delivery system controller is configured toinclude a residual gas pressure value in the calculation of therun-time-to-empty value for the therapeutic gas source.

In a fifteenth embodiment, the therapeutic gas delivery system of thefirst through fourteenth embodiments, may be modified in a mannerwherein the gas supply subsystem further comprises a gas supplysubsystem valve in between and in fluid communication with the gassource valve and the therapeutic gas flow regulator, wherein the gassupply subsystem valve is configured to maintain the therapeutic gasunder pressure between the gas supply subsystem valve and thetherapeutic gas flow regulator.

In a sixteenth embodiment, the therapeutic gas delivery system of thefirst through fifteenth embodiments, may be modified in a manner whereinthe gas supply subsystem valve is a mechanically activated check valveconfigured to be opened by a cylinder being received, wherein the gassupply subsystem valve avoids sudden release of pressure and preventsair/O2 from entering between the gas supply subsystem valve and thetherapeutic gas flow regulator.

In a seventeenth embodiment, the therapeutic gas delivery system of thefirst through sixteenth embodiments, may be modified in a manner whereinthe therapeutic gas delivery system comprises two or more gas supplysubsystems, wherein the therapeutic gas delivery system controller isconfigured to calculate the run-time-to-empty value for each therapeuticgas source in each of the two or more gas supply subsystems, and whereinthe therapeutic gas delivery system controller communicates a signal tothe gas supply subsystem valve for the therapeutic gas source calculatedto have the shortest run-time-to-empty value to transition to an openstate.

In an eighteenth embodiment, the therapeutic gas delivery system of thefirst through seventeenth embodiments, may be modified in a mannerwherein the therapeutic gas delivery system controller further comprisestwo or more subsystem controllers, wherein each of the two or more gassupply subsystems comprises one subsystem controller, and wherein eachof the two or more gas supply subsystems is configured to be controlledby the two or more subsystem controllers.

In an nineteenth embodiment, the therapeutic gas delivery system of thefirst through eighteenth embodiments, may be modified in a mannerwherein each of the two or more subsystem controllers is configured tooperate the two or more gas supply subsystems to continue delivering thetherapeutic gas if another of the two or more subsystem controllersfails.

In a twentieth embodiment, the therapeutic gas delivery system of thefirst through nineteenth embodiments may be modified in a manner whichfurther comprises a primary delivery system, further comprising a firstprimary shut off valve, wherein the first primary shut off valve is downstream from the two or more gas supply subsystems, and in fluidcommunication with the therapeutic gas flow regulators and gas pressuresensors of the two or more gas supply subsystems, a first primary highflow control valve, wherein the first primary high flow control valve isdownstream from and in fluid communication with the first primary shutoff valve, a first primary delivery flow sensor, wherein the firstprimary delivery flow sensor is downstream from and in fluidcommunication with the first primary high flow control valve, and afirst primary confirmatory flow sensor, wherein the first primaryconfirmatory flow sensor is downstream from and in fluid communicationwith the first primary delivery flow sensor.

In a twenty-first embodiment, the therapeutic gas delivery system of thefirst through twentieth embodiments may be modified in a manner whereinthe primary delivery system further comprises a second primary shut offvalve, wherein the second primary shut off valve is down stream from thetwo or more gas supply subsystems, and in fluid communication with thetherapeutic gas flow regulators and gas pressure sensors of the two ormore gas supply subsystems, a second primary high flow control valve,wherein the second primary high flow control valve is downstream fromand in fluid communication with the second primary shut off valve, asecond primary delivery flow sensor, wherein the second primary deliveryflow sensor is downstream from and in fluid communication with thesecond primary high flow control valve, and a second primaryconfirmatory flow sensor, wherein the second primary confirmatory flowsensor is downstream from and in fluid communication with the secondprimary delivery flow sensor.

In a twenty-second embodiment, the therapeutic gas delivery system ofthe first through twenty-first embodiments may be modified in a mannerwherein the first primary delivery flow sensor and the first primaryconfirmatory flow sensor are configured to measure a gas flow rate atleast when the first primary shut off valve and first primary high flowcontrol valve are in an open state, to be in communication over acommunication path with a therapeutic gas delivery system controller,and to communicate a gas flow rate value over the communication path tothe therapeutic gas delivery system controller, and wherein thetherapeutic gas delivery system controller is configured to compare thegas flow rate value from the first primary delivery flow sensor to thegas flow rate value from the first primary confirmatory flow sensor, anddetermine the difference between the two gas flow rate values.

In a twenty-third embodiment, the therapeutic gas delivery system of thefirst through twenty-second embodiments may be modified in a mannerwherein the primary delivery system is configured to provide therapeuticgas at a controlled flow rate to an injector module for wild streamblending with an air/O.sub.2 flow stream from a respirator.

In a twenty-fourth embodiment, the therapeutic gas delivery system ofthe first through twenty-third embodiments may be modified in a mannerwherein the first primary high flow control valve, first primarydelivery flow sensor, and the first primary confirmatory flow sensor areconfigured to provide a feedback control loop to adjust the flow rate oftherapeutic gas to the injector module.

In a twenty-fifth embodiment, the therapeutic gas delivery system of thefirst through twenty-fourth embodiments may be modified in a mannerwherein the therapeutic gas delivery system controller is configured toadjust the first primary high flow control valve in response to a valuereceived from the first primary delivery flow sensor to adjust the flowrate of a therapeutic gas to an intended value.

Another aspect of the present invention relates to an electronicallycontrolled gas blending device.

A first embodiment of the electronically controlled gas blending devicecomprises a flow control channel in fluid communication with atherapeutic gas supply, wherein the flow control channel comprises atleast one secondary subsystem flow control valve, wherein the at leastone secondary subsystem flow control valve is configured to be incommunication over a communication path with a therapeutic gas deliverysystem controller, and at least one secondary subsystem flow sensor,wherein the at least one secondary subsystem flow sensor is in fluidcommunication with the at least one secondary subsystem flow controlvalve, and the at least one secondary subsystem flow sensor isconfigured to be in communication over a communication path with atherapeutic gas delivery system controller, one or more inletsconfigured to connect to a gas supply, one or more inlet flow sensors influid communication with at least one of the one or more inlets, ablending junction in fluid communication with the one or more inlet flowsensors, and the blending junction is connected to and in fluidcommunication with the flow control channel, and a therapeutic gasdelivery system controller configured to be in electrical communicationwith at least the secondary subsystem flow control valve and the atleast one secondary subsystem flow sensor to form a feedback loop, andconfigured to receive a flow value from the at least one inlet flowsensors and calculate a flow rate of therapeutic gas through the atleast one secondary subsystem flow sensor to provide an intended dose oftherapeutic gas exiting the blending junction.

In a second embodiment, the electronically controlled gas blendingdevice of the first embodiment may be modified in a manner wherein theat least one secondary subsystem flow control valve and the at least onesecondary subsystem flow sensor are arranged in series along the flowcontrol channel.

In a third embodiment, the electronically controlled gas blending deviceof the first and/or second embodiments may be modified in a manner whichfurther comprises a secondary subsystem shut-off valve in fluidcommunication with the flow control channel, and wherein the secondarysubsystem shut-off valve is configured to have at least an open stateand a closed state, and to be in communication over a communication pathwith a therapeutic gas delivery system controller.

In a fourth embodiment, the electronically controlled gas blendingdevice of the first through third embodiments may be modified in amanner wherein there are two or more inlet flow sensors in fluidcommunication with at least one of the one or more inlets, and thetherapeutic gas delivery system controller is configured to receive aflow value from at least two of the two or more inlet flow sensors, andcompare the two values to determine if the two or more inlet flowsensors are providing the same flow value.

In a fifth embodiment, the electronically controlled gas blending deviceof the first through fourth embodiments may be modified in a mannerwherein there are two or more secondary subsystem flow sensors in fluidcommunication with the at least one secondary subsystem flow controlvalve, and the therapeutic gas delivery system controller is configuredto receive a flow value from at least two of the two or more secondarysubsystem flow sensors, and compare the two values to determine if thetwo or more secondary subsystem flow sensors are providing about thesame flow value.

In a sixth embodiment, the electronically controlled gas blending deviceof the first through fifth embodiments may be modified in a mannerwherein the therapeutic gas delivery system controller is configured togenerate an alarm signal if the flow values from the two of the two ormore secondary subsystem flow sensors are not about the same.

In a seventh embodiment, the electronically controlled gas blendingdevice of the first through sixth embodiments may be modified in amanner wherein the two or more inlet flow sensors are arranged in serieswith each other.

In an eighth embodiment, the electronically controlled gas blendingdevice of the first through seventh embodiments may be modified in amanner which further comprises an outlet pressure sensor in fluidcommunication with the blending junction, and configured to be incommunication over a communication path with the therapeutic gasdelivery system controller, and the outlet pressure sensor communicatespressure values to the therapeutic gas delivery system controller, andthe therapeutic gas delivery system controller is configured to detectpressure fluctuations in the outlet pressure sensor.

In a ninth embodiment, the electronically controlled gas blending deviceof the first through eighth embodiments may be modified in a mannerwhich further comprises a flow regulating valve between and in fluidcommunication with the flow control channel and the blending junction,wherein the flow regulating valve is configured to direct a flow oftherapeutic gas to either the blending junction or to an outlet.

In a tenth embodiment, the electronically controlled gas blending deviceof the first through ninth embodiments may be modified in a manner whichfurther comprises an over-pressure valve in fluid communication with theone or more inlet flow sensors and an external vent, wherein theover-pressure valve is configured to open at a predetermined pressure toavoid pressure surges from the one or more inlets to the one or moreinlet flow sensors.

In an eleventh embodiment, the electronically controlled gas blendingdevice of the first through tenth embodiments may be modified in amanner wherein the therapeutic gas delivery system controller isconfigured to receive a signal indicating a failure of another flowcontrol channel and communicate a signal to the secondary subsystemshut-off valve to transition from a closed state to an open state.

Another aspect of the present invention relates to a first embodiment ofa therapeutic gas delivery system, comprising at least one gas supplysubsystem, at least one primary gas delivery subsystem comprising atleast one primary flow control channel, at least one secondary gasdelivery subsystem comprising at least one secondary flow controlchannel comprising a secondary subsystem flow sensor, wherein thesecondary subsystem flow sensor is in fluid communication with thesecondary subsystem flow control valve, and where the secondarysubsystem flow sensor is configured to be in communication over acommunication path with a therapeutic gas delivery system controller,and a secondary subsystem flow control valve, wherein the secondarysubsystem flow control valve is in fluid communication with thesecondary subsystem shut-off valve, and the secondary subsystem shut-offvalve and secondary subsystem flow control valve are arranged in series,and a therapeutic gas delivery system controller is configured to be inelectrical communication with at least the secondary subsystem flowcontrol valve and the secondary subsystem flow sensor to form a feedbackloop.

In a second embodiment, the therapeutic gas delivery system of the firstembodiment may be modified in a manner wherein the at least one primarygas delivery subsystem is controlled by a primary gas delivery subsystemcontroller, and the at least one secondary gas delivery subsystem iscontrolled separately by a secondary gas delivery subsystem controller.

In a third embodiment, the therapeutic gas delivery system of the firstand/or second embodiments may be modified in a manner wherein thesecondary gas delivery subsystem comprises a secondary subsystemshut-off valve, wherein the secondary subsystem shut-off valve is influid communication with the therapeutic gas supply and the secondarysubsystem flow control valve, and is configured to have at least an openstate and a closed state; and the therapeutic gas delivery systemcontroller is configured to receive a failure signal from the at leastone primary gas delivery subsystem, and communicate a signal to thesecondary subsystem shut-off valve to transition from a closed state toan open state if a failure signal is received.

In a fourth embodiment, the therapeutic gas delivery system of the firstthrough third embodiments may be modified in a manner wherein thetherapeutic gas delivery system controller comprises a primary gasdelivery system controller and a secondary gas delivery systemcontroller, and the secondary gas delivery system controller isconfigured to communicate a signal to the secondary subsystem shut-offvalve to transition from a closed state to an open state to avoidinterruption of therapeutic gas flow from the therapeutic gas supply toa patient without input from a user if a failure of the primary gasdelivery system controller is detected.

In a fifth embodiment, the therapeutic gas delivery system of the firstthrough fourth embodiments may be modified in a manner which furthercomprises an outlet in fluid communication with the at least one primarygas delivery subsystem and the at least one secondary gas deliverysubsystem, wherein the at least one secondary gas delivery subsystem isconfigured to deliver a therapeutic gas to the outlet in the event of afailure of the at least one primary gas delivery subsystem.

In a sixth embodiment, the therapeutic gas delivery system of the firstthrough fifth embodiments may be modified in a manner which furthercomprises a breathing circuit comprising an injector module, wherein theinjector module is configured to be in fluid communication with arespirator and the outlet, and secondary gas delivery subsystem isconfigured to deliver a therapeutic gas to the injector module at thedose of the primary gas delivery subsystem to avoid sudden changes inthe dose of therapeutic gas.

In a seventh embodiment, the therapeutic gas delivery system of thefirst through sixth embodiments may be modified in a manner wherein theat least one primary gas delivery subsystem and the at least onesecondary gas delivery subsystem are configured to provide a flow oftherapeutic gas in parallel.

In an eighth embodiment, the therapeutic gas delivery system of thefirst through seventh embodiments may be modified in a manner whereinthe at least one secondary gas delivery subsystem further comprises aflow regulating valve between and in fluid communication with thesecondary flow control channel and a blending junction, wherein the flowregulating valve is configured to direct a flow of therapeutic gas to alow pressure outlet concurrently with flow of the therapeutic gas to theoutlet from the primary gas delivery subsystem.

In a ninth embodiment, the therapeutic gas delivery system of the firstthrough eighth embodiments may be modified in a manner wherein the flowregulating valve is configured to automatically direct a flow oftherapeutic gas to the outlet of the primary gas delivery system in theevent the primary gas delivery system fails.

In a tenth embodiment, the therapeutic gas delivery system of the firstthrough ninth embodiments may be modified in a manner which furthercomprises at least one display, wherein the therapeutic gas deliverysystem controller is configured to provide an alarm on the at least onedisplay to alert a user to the failure.

In an eleventh embodiment, the therapeutic gas delivery system of thefirst through tenth embodiments may be modified in a manner wherein thetherapeutic gas delivery system is configured to provide a regulateddose of therapeutic gas to the outlet utilizing only one functioning gassupply subsystem and only one functioning flow control channel.

Another aspect of the present invention relates to another embodiment ofan electronically controlled gas blending device, comprising a flowcontrol channel in fluid communication with a therapeutic gas supply,wherein the flow control channel comprises at least one secondarysubsystem flow control valve, wherein the at least one flow controlvalve is configured to be in communication over a communication pathwith a therapeutic gas delivery system controller, and at least twosecondary subsystem flow sensors, wherein the at least two secondarysubsystem flow sensors are in fluid communication with the at least onesecondary subsystem flow control valve, and the at least two secondarysubsystem flow sensors are configured to be in communication over acommunication path with a therapeutic gas delivery system controller,wherein the at least one secondary subsystem flow control valve and theat least two secondary subsystem flow sensors are arranged in seriesalong the flow control channel, one or more low pressure inletsconfigured to connect to a gas supply, comprising O.sub.2 and/or airfrom a wall source and/or pressurized cylinder, two or more inlet flowsensors in fluid communication with at least one of the one or more lowpressure inlets, wherein the two or more inlet flow sensors are arrangedin series with each other, a blending junction in fluid communicationwith the two or more inlet flow sensors, and the blending junction isconnected to and in fluid communication with the flow control channel,and a therapeutic gas delivery system controller comprising hardware,software, firmware, or a combination thereof, configured to be inelectrical communication with at least the secondary subsystem flowcontrol valve and the at least one of the two or more secondarysubsystem flow sensors to form a feedback loop, and configured toreceive a flow value from at least one of the two or more inlet flowsensors and calculate a flow rate of therapeutic gas through the two ormore secondary subsystem flow sensors to provide an intended dose oftherapeutic gas exiting a third leg of the blending junction.

In a second embodiment, the electronically controlled gas blendingdevice may be modified in a manner wherein an external gas supply is influid communication with one of the one or more inlets and provides aflow of air and/or oxygen (O.sub.2) to the two or more flow sensors influid communication with the one or more inlets.

Another aspect of the present invention relates to a method ofconfirming the proper functioning of a therapeutic gas delivery system.

A first embodiment relates to a method of confirming the properfunctioning of a therapeutic gas delivery system, comprisingpressurizing a gas supply subsystem at least between a gas sourceconnection valve and a closed shut off to a pressure above atmosphericpressure, monitoring the pressure between the gas source connectionvalve and the closed shut off valve with a gas pressure sensor, andpresenting an alarm if the pressure between the gas source connectionvalve and the closed shut off valve decreases over the predeterminedtime period.

In a second embodiment, the method of confirming the proper functioningof a therapeutic gas delivery system of the first embodiment may bemodified in a manner which further comprises which further comprisesmating a therapeutic gas source to a gas source coupling, and opening apurge valve in fluid communication with the gas source connection valve,and between the closed shut off and the gas source connection valve toflush gas within the gas supply subsystem with gas from the matedtherapeutic gas source.

In a third embodiment, the method of confirming the proper functioningof a therapeutic gas delivery system of the first and/or secondembodiments may be modified in a manner which further comprises mating atherapeutic gas source to a gas source coupling, and opening the shutoff to deliver a flow of therapeutic gas from the gas supply subsystemto at least one of the one or more flow control channels comprising atleast one shut off valve, at least one delivery flow sensor, and atleast one confirmatory flow sensor to purge the gas supply subsystem andthe at least one of the one or more flow control channels.

In a fourth embodiment, the method of the first through thirdembodiments may be modified in a manner which further comprises readinga gas source identifier attached to the therapeutic gas source with agas source identifier reader, wherein the gas source identifier containsinformation at least of the identity, expiration date, and theconcentration of the therapeutic gas supplied by the therapeutic gassource.

In a fifth embodiment, the method of the first through fourthembodiments may be modified in a manner which further comprisesselectively opening the shut off valve for one of the one or more flowcontrol channels, while the shut off valve for each of any other of theone or more flow control channels is closed; and measuring the gas flowrate through the at least one delivery flow sensor, and the at least oneconfirmatory flow sensor of the one flow control channel.

In a sixth embodiment, the method of the first through fifth embodimentsmay be modified in a manner which further comprises sequentially openingthe shut off valve for each of the other of the one or more flow controlchannels by selectively opening the shut off valve for the next flowcontrol channel, and closing the shut off valve of the previous flowcontrol channel.

In a seventh embodiment, the method of the first through sixthembodiments may be modified in a manner which further comprisescomparing the gas flow rate through the at least one delivery flowsensor with the gas flow rate through the at least one confirmatory flowsensor of the one flow control channel; and presenting an alarm if thereis a discrepancy between the gas flow rate through the at least onedelivery flow sensor and the gas flow rate through the at least oneconfirmatory flow sensor.

Another aspect of the invention relates to a method of confirming theproper functioning of gas delivery subsystem and injection moduleoperation.

A first embodiment relates to a method of confirming the properfunctioning of gas delivery and injection module operation, comprisingreceiving an injection module at an outlet port, providing a flow ofbreathing gas at an inlet port at a breathing gas flow rate, wherein theinlet port is in fluid communication with the outlet port, measuring thebreathing gas flow rate from the gas supply at a delivery flow sensorand at a confirmatory flow sensor, wherein the delivery flow sensor andthe confirmatory flow sensor are in fluid communication with the inletport and the outlet port, measuring the breathing gas flow rate from thegas supply at an injection module delivery flow sensor and an injectionmodule confirmatory flow sensor, wherein the injection module deliveryflow sensor and the injection module confirmatory flow sensor are influid communication with the outlet port, and determining if one of thebreathing gas flow rates measured at the confirmatory flow sensor, thedelivery flow sensor, the injection module confirmatory flow sensor, orthe injection module delivery flow sensor differs from the othermeasured breathing gas flow rates by greater than a threshold amount.

In a second embodiment, the method of confirming the proper functioningof gas delivery and injection module operation of the first embodimentmay be modified in a manner which further comprises providing an alarmif the breathing gas flow rates measured at the low pressureconfirmatory flow sensor, the low pressure delivery flow sensor, theinjection module confirmatory flow sensor, or the injection moduledelivery flow sensor differs from the other measured breathing gas flowrates by greater than a threshold amount.

In a third embodiment, the method of confirming the proper functioningof gas delivery and injection module operation of the first and/orsecond embodiments may be modified in a manner wherein the thresholdamount is about 10%.

In a fourth embodiment, the method of confirming the proper functioningof gas delivery and injection module operation of the first throughthird embodiments may be modified in a manner wherein the low pressuredelivery flow sensor and the low pressure confirmatory flow sensor arearranged in series, and wherein the injection module delivery flowsensor and the injection module confirmatory flow sensor are arranged inseries.

In a fifth embodiment, the method of confirming the proper functioningof gas delivery and injection module operation of the first throughfourth embodiments may be modified in a manner wherein the injectionmodule delivery flow sensor and the injection module confirmatory flowsensor are bi-directional flow sensors that are configured to determinethe direction of gas flow through the injection module.

In a sixth embodiment, the method of confirming the proper functioningof gas delivery and injection module operation of the first throughfifth embodiments may be modified in a manner wherein the low pressuregas supply comprises a wall supply and/or a pressurized cylinderconfigured to provide air, oxygen, or a combination thereof.

In a seventh embodiment, the method of confirming the proper functioningof gas delivery and injection module operation of the first throughsixth embodiments may be modified in a manner which further comprisesproviding a stream of therapeutic gas to the flow of breathing gasupstream from an output of the injection module, wherein the stream oftherapeutic gas and breathing gas combine to provide an intendedconcentration of therapeutic gas.

In an eighth embodiment, the method of confirming the proper functioningof gas delivery and injection module operation of the first throughseventh embodiments may be modified in a manner which further comprisesconnecting a sampling line down stream from the output of the injectionmodule to sample at least a portion of the flow of gas exiting theinjection module to a gas analyzer for measurement of at least theconcentration of therapeutic gas, determining the concentration oftherapeutic gas exiting the injection module, and comparing the measuredconcentration of therapeutic gas with the intended concentration oftherapeutic gas.

In a ninth embodiment, the method of confirming the proper functioningof gas delivery and injection module operation of the first througheighth embodiments may be modified in a manner which further comprisesadjusting a subsystem flow control valve to provide a stream oftherapeutic gas at an intended therapeutic gas flow rate; anddetermining if the subsystem flow control valve is properly functioning,wherein the subsystem flow control valve is in fluid communication withthe low pressure outlet port.

In a tenth embodiment, the method of confirming the proper functioningof gas delivery and injection module operation of the first throughninth embodiments may be modified in a manner which further comprisesmeasuring the combined therapeutic gas flow rate and breathing gas flowrate at the injection module delivery flow sensor and the injectionmodule confirmatory flow sensor, switching a flow regulating valve todivert the stream of therapeutic gas to an alternative flow path,wherein the flow regulating valve is up stream from and in fluidcommunication with the low pressure outlet port, and the subsystem flowcontrol valve is upstream from and in fluid communication with the flowregulating valve, measuring the breathing gas flow rate at the injectionmodule delivery flow sensor and the injection module confirmatory flowsensor, and determining if the flow regulating valve functioned properlyby determining if the combined therapeutic gas flow rate and breathinggas flow rate decreased by the therapeutic gas flow rate when the flowregulating valve was switched to the alternative flow path.

In an eleventh embodiment, the method of confirming the properfunctioning of gas delivery and injection module operation of the firstthrough tenth embodiments may be modified in a manner which furthercomprises measuring a flow rate at two or more subsystem flow sensors,wherein the two or more subsystem flow sensors are upstream from and influid communication with the three-way valve; and comparing the flowrates measured at each of the two or more subsystem flow sensors todetermine if the two or more subsystem flow sensors are in agreement.

In a twelfth embodiment, the method of confirming the proper functioningof gas delivery and injection module operation of the first througheleventh embodiments may be modified in a manner which further comprisescalculating therapeutic gas blending ratio from the measured flow ratemeasured by at least one of the two or more subsystem flow sensors andfrom the breathing gas flow rate measured by the low pressure deliveryflow sensor; and comparing the calculated therapeutic gas blending ratioto the measured concentration of therapeutic gas exiting the injectionmodule.

In a thirteenth embodiment, the method of confirming the properfunctioning of gas delivery and injection module operation of the firstthrough twelfth embodiments may be modified in a manner which furthercomprises adjusting a subsystem flow control valve to be completely opento provide the stream of therapeutic gas at a maximum therapeutic gasflow rate.

Another aspect of the invention relates to a method to ensure the properfunctioning of a therapeutic gas delivery system.

A first embodiment relates to a method to ensure the proper functioningof a therapeutic gas delivery system, comprising detecting a therapeuticgas source mated with a therapeutic gas supply subsystem, providing aninitial purge of the therapeutic gas supply subsystem with gas from thetherapeutic gas source, determining if the initial purge was successful,maintaining a shutoff valve down stream from the therapeutic gas sourcein a closed state, verifying that no flow is detected by one or moreflow sensors down stream from the shutoff valve, and determining if flowis detected by one or more flow sensors down stream from the shutoffvalve; and providing an alert if it is determined that the initial purgewas not successful and/or if flow is detected by one or more flowsensors down stream from the shutoff valve.

In a second embodiment, the method to ensure the proper functioning of atherapeutic gas delivery system of the first embodiment may be modifiedin a manner which further comprises reading information associated withthe therapeutic gas source to determine the identity, concentration,and/or expiration date of the therapeutic gas source, and verifying thetherapeutic gas source mated with a therapeutic gas supply subsystem hasthe correct identity, concentration, and/or expiration date.

In a third embodiment, the method to ensure the proper functioning of atherapeutic gas delivery system of the first and/or second embodimentsmay be modified in a manner wherein the shutoff valve down stream fromthe therapeutic gas source in a closed state until the correct identity,concentration, and/or expiration date is verified.

The systems and methods may further comprise an alarm system to informthe user when a therapeutic gas source has reached a predeterminedminimum run-time-to-empty. In various systems in which multiple therapygas sources are engaged, the alarm system may also inform the user witha high-priority alarm when the total run-time-to-empty of the system hasbeen reached.

BRIEF DESCRIPTION OF THE DRAWINGS

The features and advantages of the present invention will be more fullyunderstood with reference to the following, detailed description whentaken in conjunction with the accompanying figures, wherein:

FIG. 1 is an overview diagram of an exemplary therapeutic gas deliverysystem and patient breathing apparatus, in accordance with exemplaryembodiments of the present invention;

FIG. 2 is a diagram of the exemplary therapeutic gas delivery system, inaccordance with exemplary embodiments of the present invention;

FIG. 3 is a diagram of the portion of the exemplary therapeutic gasdelivery system downstream of FIG. 2 and/or which couples to the patientbreathing apparatus, in accordance with exemplary embodiments of thepresent invention;

FIGS. 4A-4C is a flow chart of an exemplary pre-use performancevalidation process, in accordance with exemplary embodiments of thepresent invention;

FIG. 5 is a diagram of an exemplary arrangement of a therapeutic gasdelivery system for use during exemplary embodiments of a pre-useperformance validation process; and

FIG. 6 is a flow chart of an exemplary process for determining whethervarious sensors are properly calibrated, in accordance with exemplaryembodiments of the present invention.

DETAILED DESCRIPTION

In exemplary embodiments, systems and methods of the present inventionprovide enhanced safety improvements over current therapeutic gasdelivery systems by at least enabling accurate and/or precisedetermination and/or usage of information indicative of therun-time-to-empty for the therapeutic gas source. In exemplaryembodiments, a plurality of therapeutic gas sources can be affiliatedwith a therapeutic gas delivery system. Further, in at least someinstances, the present invention can determine and/or use informationindicative of the run-time-to-empty for a plurality of therapeutic gassources affiliated with a therapeutic gas delivery system.

In exemplary embodiments, therapeutic gas delivery systems of thepresent invention can comprise at least one gas supply subsystem, atleast one primary delivery subsystem, and/or at least one secondarydelivery subsystem, wherein redundant systems and/or components provideparallel or supplemental data enabling cross verification of componentoperation, fallback functionality, and/or fail-safe protection of thepatient and the system. In at least some embodiments, the presentinvention can provide simplified therapeutic gas delivery systems andmethods of fail-safe protection and redundancy that can allow seamlesstransition to backup systems automatically, for example, without theneed of extensive training of a user. Further, in exemplary embodiments,the present invention can mitigate risks associated with suddentermination of inhaled therapeutic gas delivery and/or incorrectdelivery of therapy.

In one or more embodiments, therapeutic gas delivery systems of thepresent invention can comprise, amongst other things, at least one gassupply subsystem as well as at least one least one gas deliverysubsystem. For example, therapeutic gas delivery systems of the presentinvention can comprise at least one gas supply subsystem and at leastone delivery subsystem comprising at least one flow control channel,wherein the gas supply subsystem provides a first therapeutic gas sourcehaving a volume and/or containing a therapeutic gas at an initialpressure for delivery to a patient. For another example, therapeutic gasdelivery systems of the present invention can comprise two or more gassupply subsystems, a primary delivery subsystem having at least one flowcontrol channel comprising a plurality of valves and a plurality of flowsensors, and a secondary delivery subsystem having at least one flowcontrol channel comprising a plurality of valves and a plurality of flowsensors, wherein the two or more gas supply subsystems provide a firsttherapeutic gas source having a volume and/or containing a therapeuticgas at an initial pressure for initial delivery of therapeutic gas to apatient, and at least a second therapeutic gas source having a volumeand/or containing a therapeutic gas at an initial pressure forsubsequent delivery of therapeutic gas to a patient when the pressurewithin the first therapeutic gas source falls below a predetermined,threshold value.

In various embodiments, the primary delivery subsystem and/or thesecondary delivery subsystem control the flow rate of therapeutic gas toachieve the set dose being delivered to a patient in need of thetherapeutic gas, and, in at least some instances, the therapeutic gasmay be blended with air and/or oxygen before being received by thepatient.

In exemplary embodiments, systems and methods can determine the lengthof time that a therapeutic gas source can continue delivering thetherapeutic gas before having insufficient pressure/gas volume, alsoreferred to as “run-time-to-empty”, for example, by calculating thevolume and pressure of therapeutic gas available from the therapeuticgas source, for example by using the ideal gas law, and the rate atwhich the therapeutic gas is flowing from the therapeutic gas source. Asused herein, “run-time-to-empty”, “RTE”, or the like means the estimatedtime a therapeutic gas source can continue to supply the therapeutic gasat a current flow rate until the pressure remaining in the therapeuticgas source reaches a threshold value at which the ability to control ormaintain the flow rate may be affected.

In one or more embodiments, a therapeutic gas delivery system comprisingtwo or more therapeutic gas sources may first supply therapeutic gasfrom the therapeutic gas source having the shorter run-time-to-emptyvalue and/or minimum run-time pressure. In various embodiments, thetherapeutic gas delivery system may seamlessly transition from a firsttherapeutic gas source to a second therapeutic gas source when the firsttherapeutic gas source has reached the intended run-time-to-empty valueand/or minimum run-time pressure. For example, systems and methods canenable source gas cut-over (e.g., seamless transition) between at leasttwo source gases (e.g., therapeutic gas being received for delivery fromone gas source can be halted such that the therapeutic gas can bereceived for delivery from another gas source) when run-time-to-emptyfor a therapeutic gas source is below a minimum threshold and/or whendesired. In one or more embodiments, cut-over may be accomplishedwithout any interruption of therapeutic gas flow, where cut-over mayinvolve controller actuated opening of a flow path to a subsequenttherapeutic gas source before closing, immediately after closing, and/orin parallel with closing the flow path to the initial therapeutic gassource to avoid sudden interruption of gas inhalation therapy, which mayalso be referred to as “seamless transition.” In at least someembodiments, usage of the therapeutic gas source may not be allowed ifthe source does not have a minimum run-time pressure (e.g., pressurebelow 300 psi, not enough pressure to perform purges, pressure low orwaning indicative of leak, etc.).

In various embodiments, the therapeutic gas source having the shorterrun-time-to-empty value is used first to provide sufficient time toreplace the exhausted therapeutic gas source before the secondtherapeutic gas source may become exhausted. In various embodiments, auser may be alerted to the run-time-to-empty value, a need to switchover to another therapeutic gas source, and/or the need to replace aneffectively empty therapeutic gas source, for example, after switch-overto a second therapeutic gas source provided as a backup to avoid suddendiscontinuation of the therapeutic inhalation therapy. In embodimentswherein the therapeutic gas delivery system is configured to engagemultiple therapeutic gas sources, the program or algorithm incorporatesthe number of therapeutic gas sources connected to the system into therun-time-to-empty calculation. For example, run-time-to empty iscalculated in the manner described above for each connected therapeuticgas source and the program or algorithm uses this data to calculate atotal run-time-to-empty for the therapeutic gas delivery system for useof each therapeutic gas source sequentially. Sequential use of multipletherapeutic gas sources connected to the therapeutic gas delivery systemmeans that a first therapeutic gas source is in fluid communication withthe therapeutic gas supply system and at least a second therapeutic gassource is connected to another therapeutic gas supply system, but isshut off from fluid communication to one or more therapeutic gasdelivery system(s).

Principles and embodiments or the present invention also relate toalgorithms to obtain values from sensor(s), valve(s), regulator(s),and/or detector(s), and perform the calculations of run-time-to-emptybased on the obtained values. In various embodiments, values may becommunicated from sensors, valves, regulators, and/or detectors, to thetherapeutic gas delivery system controller, where the value may becommunicated as an analog or digital signal over a communication paththat may be wired or wireless. In various embodiments, a value may beelectrically communicated as an analog current and/or voltage, or as adigital sequence that is representative of the value, where thetherapeutic gas delivery system controller may be configured to receive,interpret, and/or store the value, for example with A-to-D converters,buffers, direct memory access (DMA), as well as other hardware,software, and/or firmware that is known in the art.

In exemplary embodiments, an algorithm can determine the run-time-toempty (RTE) using gas pressure information, therapeutic gas sourcevolume information, temperature information, and equations. RTE can becalculated by a therapeutic gas delivery system controller withinformation generated from using (i) Delivery NO flow sensors, (ii)Redundant (monitoring) flow sensors, (iii) Commands/Settings to NOcontrol valve, (iv) Set dose+Injector module (IM) flow sensor reading(delivery or redundant monitoring flow sensor); and/or (v) Gas sourcecontents pressure sensing.

In exemplary embodiments, RTE can account for (i) Purging (current andfuture) using therapeutic gas; (ii) System level leaks determined byhigh pressure or lower (32) pressure decay test; (iii) Residual pressureintended to be left in gas source (gas source not emptied completely);(iv) Concurrent delivery—secondary and Primary running at same time; (v)temperature (e.g., temperature changes may result in changes inpressure, etc.); (vii) filtering (e.g., undesired oscillating values maybe filtered, RTE displayed may filter out oscillations, (vi) RTE lifeextension can immediately update upon changes in set dose; and/or (vii)Improved RTE accuracy with ambient temperature correction.

In one or more embodiments, run-time-to empty information and/or alarmscan be provided to users of the therapeutic gas delivery system for oneor more of the therapeutic gas sources. In various embodiments,run-time-to empty information and/or alarms may be displayed on adisplay screen affiliated with one of the one or more gas supplysubsystems. In various embodiments, a separate display screen may beaffiliated with each of the two or more gas supply subsystems, whereeach of the displays may be configured to present run-time-to emptyinformation and/or alarms to a user.

Principles and embodiments of the present invention also generallyrelate to a therapeutic gas delivery system comprising automatic back-upsystems that provide simple and easy to use therapeutic gas delivery inthe event of failure of a primary gas delivery system, where a back-upsystem for manual ventilation (e.g., bagging, external manualventilation device, assisted breathing apparatus, etc.) is sufficientlyautomated and simple to be utilized by personnel that are otherwiseuntrained on therapeutic gas delivery systems. In one or moreembodiments, a therapeutic gas blending system is configured to providea controlled gas flow rate to an external manual ventilation device(e.g., bag valve mask) for providing the same set dose to allow apatient to remain ventilated without discontinuation of inhalationtherapy.

Delivery and Sampling System Overview

Referring to FIGS. 1-3 , an exemplary system for delivering inhaledtherapeutic nitric oxide gas (NO) to a patient is illustrativelydepicted. It will be understood that systems and methods of the presentinvention can use, modify, and/or be affiliated with any applicablesystem for delivering therapeutic gas to a patient. For example, systemsand methods of the present invention can use, modify, and/or beaffiliated with the delivery systems and/or other teachings of U.S. Pat.No. 5,558,083 entitled “NO Delivery System” and/or U.S. Pat. No.5,752,504 entitled “System for Monitoring Therapy During Calibration”,the contents of both of which are incorporated herein by reference intheir entireties.

Systems and methods are, at times, described as being directed towardsinhaled nitric oxide (NO). This is merely for ease and is in no waymeant to be a limitation. Of course the teachings disclosed herein can,when appropriate, be used for other therapeutic gas, such as, but notlimited to, carbon monoxide (CO), hydrogen sulfide (H.sub.2S), etc.Further, therapeutic gas can be supplied from one or more therapeuticgas sources that can be any source of therapeutic gas such as atherapeutic gas contained in a cylinder (e.g., a cylinder containing NO,H.sub.2S), NO gas generator, or the like. Of course other sources oftherapeutic gas can be used. For ease, at times, the therapeutic gassource is described as a cylinder, NO cylinder, and the like. This ismerely for ease and is in no way meant to be a limitation.

In exemplary embodiments, a therapeutic gas delivery system 100 can beused to deliver therapeutic gas, such as NO, to a patient 203 who may beusing an assisted breathing apparatus such as a ventilator 205 or otherdevice used to introduce therapeutic gas to the patient, for example, anasal cannula, endotracheal tube, face mask, bag valve mask, or thelike. For ease, systems and methods of the present invention aredescribed, at times, as being for use with a ventilator. This is merelyfor ease and is in no way meant to be a limitation. For example, for atleast a ventilated patient 203, ventilator 205 can deliver breathing gasto patient 203 via inspiratory limb 213 of patient breathing circuit209, while patient expiration can flow via an expiratory limb 215 ofpatient breathing circuit 209, at times, to ventilator 205. Of courseother ventilator types are envisioned. For example, a single limbventilator type system is envisioned that may have a combinedinspiratory and expiratory limb.

In exemplary embodiments, systems and methods of the present inventioncan be used to wild stream blend therapeutic gas with inspiratory flow(e.g., provided from a ventilator, provided from an air and/or oxygensource, etc.). By way of example, described below in more detail, wildstream blending can be accomplished with an injector module 107 coupledto inspiratory limb 213 of breathing circuit 209 enabling NO to bedelivered from therapeutic gas delivery system 100 and/or any subsystem(e.g., primary gas delivery subsystem, secondary gas delivery system,etc.) to injector module 107, via delivery conduit 111. This NO can thenbe delivered, via injector module 107, into inspiratory limb 213 ofpatient breathing circuit 209 affiliated with ventilator 205 being usedto deliver breathing gas to a patient 203. By way of another example,described below in more detail, wild stream blending can be accomplishedby blending NO with air and/or oxygen provided from a wall outlet (e.g.,high pressure air and/or oxygen that may be provided from a wall outletin a hospital or cylinder supply, low pressure air and/or oxygen thatmay be provided from a regulator that may receive air and/or oxygen froma wall outlet in a hospital, gas compressor outlet, etc.). In at leastsome instances, wild stream blending (e.g., NO with air and/or oxygenprovided from a wall outlet) can occur within system 100. In exemplaryembodiments, wild stream blending can occur internally within system 100and/or external of system 100, for example, at injector module 107.

As used herein, “wild stream blended proportional”, “wild streamblending”, “ratio metric blending”, and the like, relates to streamblending, where the main flow stream is an uncontrolled (unregulated)stream that is referred to as the wild stream, and the component beingintroduced into the wild stream is controlled as a proportion of themain stream, which may typically be blended upstream (or alternativelydownstream) of the main stream flowmeter. In various embodiments, theinspiratory flow may be the “wild stream” as the flow (e.g., from theventilator) is not specifically regulated or controlled by thetherapeutic gas delivery system, and the nitric oxide is the blendcomponent, for example, that may be delivered as a proportion of theinspiratory flow through the delivery line and/or conduit 111.

In exemplary embodiments, to at least wild stream blend NO, injectormodule 107 can be affiliated with at least one flow sensor capable ofmeasuring the mass and/or volume flow rate(s) of at least patientbreathing gas in the inspiratory line of the patient breathing circuit.For example, injector module 107 can include one or more breathingcircuit gas (BCG) flow sensors 108(a) and/or 108(b) that can measure andcommunicate to the NO delivery system and/or any subsystem (e.g. primarydelivery subsystem, secondary delivery subsystem, etc.) the mass and/orvolume flow rate(s) of at least patient breathing gas in the inspiratoryline of the breathing circuit passing through injector module 107, andin turn to patient 203. BCG flow sensors may be bi-directional. BCGsensors may also operate via differential pressure measurements.Although shown as being at injector module 107, BCG flow sensors 108(a)and/or 108(b) can be placed elsewhere in the inspiratory limb 213, suchas upstream of the injector module 107. Also, instead of receiving flowinformation from BCG flow sensors 108(a) and/or 108(b), the deliverysystem may receive flow information directly from the source ofinspiratory flow (e.g., ventilator 205, high pressure air and/or oxygenthat may be provided from a wall outlet in a hospital, low pressure airand/or oxygen that may be provided from a regulator that may receive airand/or oxygen from a wall outlet in a hospital, etc.) indicative of theflow of breathing gas from the source of inspiratory flow (e.g.,ventilator 205, high pressure air and/or oxygen that may be providedfrom a wall outlet in a hospital, low pressure air and/or oxygen thatmay be provided from a regulator that may receive air and/or oxygen froma wall outlet in a hospital, etc.).

Therapeutic gas delivery system 100 can include, amongst other things, afirst gas supply subsystem 110(a), a second gas supply subsystem 110(b),a primary gas delivery subsystem 140, a secondary gas delivery subsystem160, and/or a gas analyzing subsystem 180. Therapeutic gas deliverysystem 100 can also include user interfaces such as display(s) 102and/or user input interface(s) 106. Further, first gas supply subsystem110(a) can have user interfaces such as display 112(a) and/or second gassupply subsystem 110(b) can have user interfaces such as display 112(b).Any of the user interfaces can include, but is not limited to buttons,keyboards, knobs, and/or touchscreens, to name a few and/or user inputinterfaces and/or displays can be combined such that information can beinput by users and/or communicated to users. By way of example, userinput interface 102, 106 and/or displays 112(a), 112(b) can receiveand/or provide information indicative of desired settings from the user,such as, but not limited to, the patient's prescription (in mg/kg idealbody weight, mg/kg/hr, mg/kg/breath, mL/breath, gas sourceconcentration, delivery concentration or set dose, duration, etc.), thepatient's age, height, sex, weight, etc. User input interface 102, 106and/or display 112(a), 112(b) may be configured in at least someinstances be used to confirm the desired patient dosing (e.g., userinput desired dose of NO PPM) using a gas sampling subsystem 180, asdescribed in greater detail below. In various embodiments, thetherapeutic gas delivery system 100 may be in communication with themedical facility's (e.g., hospital) patient information system, wherethe patient's information and/or prescription can be directlycommunicated from the patient information system to the therapeutic gasdelivery system 100.

It will be understood that any of the elements of system 100 can becombined and/or further separated. For ease elements are, at times,described as being specific to subsystems. This is merely for ease andis in no way meant to be a limitation. Further, informationcommunication paths are, at times, illustrated as dashed lines and/orfluid communication conduits are, at times, illustrated as solid lines.This is merely for ease and is in no way meant to be a limitation.

To at least deliver desired set doses of therapeutic gas to a patient,sample therapeutic gas being delivered to a patient, and/or performother methods and operations, therapeutic gas delivery system 100 caninclude a system controller (not shown) and/or subsystems can includesubsystem controllers such as, but not limited to, gas supply subsystemcontroller 129(a), gas supply subsystem controller 129(b), primary gasdelivery subsystem controller 144, a secondary gas delivery subsystemcontroller 164, and/or a gas analyzing subsystem(s) controller 184. Thesystem controller and/or any of the subsystem controllers may compriseone or more processors (e.g., CPUs) and memory, where the systemcontroller and/or any of the subsystem controllers may comprise, forexample, a computer system, a single board computer, one or moreapplication-specific integrated circuits (ASICs), or a combinationthereof. Processors can be coupled to memory and may be one or more ofreadily available memory such as random access memory (RAM), read onlymemory (ROM), flash memory, compact/optical disc storage, hard disk, orany other form of local or remote digital storage. Support circuits canbe coupled to processors, to support processors, sensors, valves,analyzing systems, delivery systems, user inputs, displays, injectormodules, breathing apparatus, etc. in a conventional manner. Thesecircuits can include cache memory, power supplies, clock circuits,input/output circuitry, analog-to-digital and/or digital-to-analogconvertors, subsystems, power controllers, signal conditioners, and thelike. Processors and/or memory can be in communication with sensors,valves, analyzing systems, delivery systems, user inputs, displays,injector modules, breathing apparatuses, etc. Communication to and fromthe system controller may be over a communication path, where thecommunication path may be wired or wireless, and wherein suitablehardware, firmware, and/or software may be configured to interconnectcomponents and/or provide electrical communications over thecommunication path(s).

In various embodiments, primary gas delivery subsystem controller 144and secondary gas delivery subsystem controller 164 may be redundantcontrollers with duplicate hardware, software and/or firmware (e.g.,architected to function with redundancies, etc.), where each subsystemcontroller can perform the operations of the other subsystem controllerand take over in the event of a failure. In various embodiments,therapeutic gas delivery system controller comprises primary gasdelivery subsystem controller 144 and secondary gas delivery subsystemcontroller 164, where primary gas delivery subsystem controller 144and/or secondary gas delivery subsystem controller 164 may be mastercontrollers and gas supply subsystem controller 129(a) and/or gas supplysubsystem controller 129(b) may be slave controllers. In variousembodiments, gas analyzer subsystem controller 184 may be a slavecontroller under primary gas delivery subsystem controller 144 and/orsecondary gas delivery subsystem controller 164. Of course, other masterslave configurations are and/or other controller configurations areenvisioned.

In various embodiments, the therapeutic gas delivery system controllercan comprise, but is not limited to, at least one of four subsystemcontrollers 144, 164, 129(a), and/or 129(b). In exemplary embodiments,each subsystem controller for each subsystem is in electricalcommunication with components of that subsystem, components of othersubsystems and/or any other components affiliated with system 100.

For example, subsystem controller 129(a) can be in electricalcommunication with the components of a first gas supply subsystem 110(a)(e.g., received therapeutic gas source 116(a), therapeutic gas sourcevalve 117(a), gas source connection valve 118(a), gas pressure sensor120(a), pressure regulator 122(a), purge valve 124(a), shut off 126(a),gas source identifier 128(a), temperature sensor 130(a), gas sourceidentifier reader 131(a), and/or gas source detector 132(a), etc.),and/or components of another subsystem such as second gas supplysubsystem 110(b) (e.g., received therapeutic gas source 116(b),therapeutic gas source valve 117(b), gas source connection valve 118(b),gas pressure sensor 120(b), pressure regulator 122(b), purge valve124(b), shut off 126(b), gas source identifier 128(b), temperaturesensor 130(b), gas source identifier reader 131(b), and/or gas sourcedetector 132(b), etc.), primary gas delivery subsystem 140 (e.g., firstprimary shut off valve 142(a), first primary high flow control valve143(a), first primary delivery flow sensor 146(a), first primaryconfirmatory flow sensor 148(a), second primary shut off valve 142(b),second primary high flow control valve 143(b), second primary deliveryflow sensor 146(b), and/or second primary confirmatory flow sensor148(b), etc.), secondary gas delivery subsystem 160 (e.g., secondaryshut off valve 162, secondary medium flow control valve 163, secondarydelivery flow sensor 166, and/or a secondary confirmatory flow sensor168, flow regulating valve 170, low pressure oxygen/air received flowsensor 174, low pressure oxygen/air received confirmatory flow sensor176, low pressure oxygen/air received pressure sensor 178, and/oroverpressure valve 179, etc.), gas analyzing subsystem(s) 180 (e.g., gassensor 182, gas sensor 186, gas sensor 188, sample gas flow sensor 190;sample pump 192; and/or sample system valve(s) 194, etc.), and/or anyother components affiliated with system 100 (e.g., injector moduledelivery flow sensor 108(a), injector module confirmatory flow sensor108(b)).

For another example, subsystem controllers 129(b) is in electricalcommunication with the components of a second gas supply subsystem110(b) (e.g., received therapeutic gas source 116(b), therapeutic gassource valve 117(b), gas source connection valve 118(b), gas pressuresensor 120(b), pressure regulator 122(b), purge valve 124(b), shut off126(b), gas source identifier 128(b), temperature sensor 130(b), gassource identifier reader 131(b), and/or gas source detector 132(b),etc.), and/or components of another subsystem such as second gas supplysubsystem 110(a) (e.g., received therapeutic gas source 116(a),therapeutic gas source valve 117(a), gas source connection valve 118(a),gas pressure sensor 120(a), pressure regulator 122(a), purge valve124(a), shut off 126(a), gas source identifier 128(a), temperaturesensor 130(a), gas source identifier reader 131(a), and/or gas sourcedetector 132(a), etc.), primary gas delivery subsystem 140 (e.g., firstprimary shut off valve 142(a), first primary high flow control valve143(a), first primary delivery flow sensor 146(a), first primaryconfirmatory flow sensor 148(a), second primary shut off valve 142(b),second primary high flow control valve 143(b), second primary deliveryflow sensor 146(b), and/or second primary confirmatory flow sensor148(b), etc.), secondary gas delivery subsystem 160 (e.g., secondaryshut off valve 162, secondary medium flow control valve 163, secondarydelivery flow sensor 166, and/or a secondary confirmatory flow sensor168, flow regulating 3-way valve 170, low pressure oxygen/air receivedflow sensor 174, low pressure oxygen/air received confirmatory flowsensor 176, low pressure oxygen/air received pressure sensor 178, and/oroverpressure valve 179, etc.), gas analyzing subsystem(s) 180 (e.g., gassensor 182, gas sensor 186, gas sensor 188, sample gas flow sensor 190;sample pump 192; and/or sample system valve(s) 194, etc.), and/or anyother components affiliated with system 100 (e.g., injector moduledelivery flow sensor 108(a), injector module confirmatory flow sensor108(b)).

For another example, subsystem controllers 144 is in electricalcommunication with the components of primary gas delivery subsystem 140(e.g., first primary shut off valve 142(a), first primary high flowcontrol valve 143(a), first primary delivery flow sensor 146(a), firstprimary confirmatory flow sensor 148(a), second primary shut off valve142(b), second primary high flow control valve 143(b), second primarydelivery flow sensor 146(b), and/or second primary confirmatory flowsensor 148(b), etc.) and/or components of another subsystem such asfirst gas supply subsystem 110(a) (e.g., received therapeutic gas source116(a), therapeutic gas source valve 117(a), gas source connection valve118(a), gas pressure sensor 120(a), pressure regulator 122(a), purgevalve 124(a), shut off 126(a), gas source identifier 128(a), temperaturesensor 130(a), gas source identifier reader 131(a), and/or gas sourcedetector 132(a), etc.), second gas supply subsystem 110(b) (e.g.,received therapeutic gas source 116(b), therapeutic gas source valve117(b), gas source connection valve 118(b), gas pressure sensor 120(b),pressure regulator 122(b), purge valve 124(b), shut off 126(b), gassource identifier 128(b), temperature sensor 130(b), gas sourceidentifier reader 131(b), and/or gas source detector 132(b), etc.),primary gas delivery subsystem 140 (e.g., first primary shut off valve142(a), first primary high flow control valve 143(a), first primarydelivery flow sensor 146(a), first primary confirmatory flow sensor148(a), second primary shut off valve 142(b), second primary high flowcontrol valve 143(b), second primary delivery flow sensor 146(b), and/orsecond primary confirmatory flow sensor 148(b), etc.), secondary gasdelivery subsystem 160 (e.g., secondary shut off valve 162, secondarymedium flow control valve 163, secondary delivery flow sensor 166,and/or a secondary confirmatory flow sensor 168, flow regulating valve170, low pressure oxygen/air received flow sensor 174, low pressureoxygen/air outlet confirmatory flow sensor 176, low pressure oxygen/airreceived pressure sensor 178, and/or overpressure valve 179, etc.), gasanalyzing subsystem(s) 180 (e.g., gas sensor 182, gas sensor 186, gassensor 188, sample gas flow sensor 190; sample pump 192; and/or samplesystem valve(s) 194, etc.), and/or any other components affiliated withsystem 100 (e.g., delivery flow sensor 108(a), injector moduleconfirmatory flow sensor 108(b)).

For another example, subsystem controller 164 is in electricalcommunication with the components of secondary gas delivery subsystem160 (e.g., secondary shut off valve 162, secondary medium flow controlvalve 163, secondary delivery flow sensor 166, and/or a secondaryconfirmatory flow sensor 168, flow regulating valve 170, low pressureoxygen/air received flow sensor 174, low pressure oxygen/air receivedconfirmatory flow sensor 176, low pressure oxygen/air received pressuresensor 178, and/or overpressure valve 179, etc.) and/or components ofanother subsystem such as first gas supply subsystem 110(a) (e.g.,received therapeutic gas source 116(a), therapeutic gas source valve117(a), gas source connection valve 118(a), gas pressure sensor 120(a),pressure regulator 122(a), purge valve 124(a), shut off 126(a), gassource identifier 128(a), temperature sensor 130(a), gas sourceidentifier reader 131(a), and/or gas source detector 132(a), etc.),second gas supply subsystem 110(b) (e.g., received therapeutic gassource 116(b), therapeutic gas source valve 117(b), gas sourceconnection valve 118(b), gas pressure sensor 120(b), pressure regulator122(b), purge valve 124(b), shut off 126(b), gas source identifier128(b), temperature sensor 130(b), gas source identifier reader 131(b),and/or gas source detector 132(b), etc.), primary gas delivery subsystem140 (e.g., first primary shut off valve 142(a), first primary high flowcontrol valve 143(a), first primary delivery flow sensor 146(a), firstprimary confirmatory flow sensor 148(a), second primary shut off valve142(b), second primary high flow control valve 143(b), second primarydelivery flow sensor 146(b), and/or second primary confirmatory flowsensor 148(b), etc.), gas analyzing subsystem(s) 180 (e.g., gas sensor182, gas sensor 186, gas sensor 188, sample gas flow sensor 190; samplepump 192; and/or sample system valve(s) 194, etc.), and/or any othercomponents affiliated with system 100 (e.g., injector module deliveryflow sensor 108(a), injector module confirmatory flow sensor 108(b)).

For another example, subsystem controller 184 is in electricalcommunication with the components of gas analyzing subsystem(s) 180(e.g., gas sensor 182, gas sensor 186, gas sensor 188, sample gas flowsensor 190; sample pump 192; and/or sample system valve(s) 194, etc.),and/or any other components affiliated with system 100 (e.g., injectormodule delivery flow sensor 108(a), injector module confirmatory flowsensor 108(b)) and/or components of another subsystem such as first gassupply subsystem 110(a) (e.g., received therapeutic gas source 116(a),therapeutic gas source valve 117(a), gas source connection valve 118(a),gas pressure sensor 120(a), pressure regulator 122(a), purge valve124(a), shut off 126(a), gas source identifier 128(a), temperaturesensor 130(a), gas source identifier reader 131(a), and/or gas sourcedetector 132(a), etc.), second gas supply subsystem 110(b) (e.g.,received therapeutic gas source 116(b), therapeutic gas source valve117(b), gas source connection valve 118(b), gas pressure sensor 120(b),pressure regulator 122(b), purge valve 124(b), shut off 126(b), gassource identifier 128(b), temperature sensor 130(b), gas sourceidentifier reader 131(b), and/or gas source detector 132(b), etc.),primary gas delivery subsystem 140 (e.g., first primary shut off valve142(a), first primary high flow control valve 143(a), first primarydelivery flow sensor 146(a), first primary confirmatory flow sensor148(a), second primary shut off valve 142(b), second primary high flowcontrol valve 143(b), second primary delivery flow sensor 146(b), and/orsecond primary confirmatory flow sensor 148(b), etc.), secondary gasdelivery subsystem 160 (e.g., secondary shut off valve 162, secondarymedium flow control valve 163, secondary delivery flow sensor 166,and/or a secondary confirmatory flow sensor 168, flow regulating valve170, low pressure oxygen/air received flow sensor 174, low pressureoxygen/air received confirmatory flow sensor 176, low pressureoxygen/air received pressure sensor 178, and/or overpressure valve 179,etc.), and/or any other components affiliated with system 100 (e.g.,injector module delivery flow sensor 108(a), injector moduleconfirmatory flow sensor 108(b)).

In one or more embodiments, each subsystem controller 129(a), 129(b),144, 164, 184 communicates with each of the other subsystem controllers129(a), 129(b), 144, 164, 184 and at least therapeutic gas deliverysystem controllers 144, 164 are configured to detect faults, errors,and/or failures, including complete subsystem controller failure. Invarious embodiments, therapeutic gas delivery system controllers 144,164 are configured to take over operation of another subsystemcontroller if and when a fault, error, and/or failure is detected.

The clock circuits may be internal to the system controller and/orprovide a measure of time relative to an initial start, for example onboot-up. The system may comprise a real-time clock (RTC) that providesactual time, which may be synchronized with a time-keeping source, forexample a network. The memory may be configured to receive and storevalues for calculations and/or comparison to other values, for examplefrom sensor(s), pumps, valves, etc.

In exemplary embodiments, the memory may store a set ofmachine-executable instructions (or algorithms), when executed byprocessors, that can cause the therapeutic gas delivery system and/orany of the subsystems (e.g., functioning independently of one another,any of the subsystems functioning in concert, etc.) to perform variousmethods and operations.

For example, the delivery subsystems 140, 160 can perform methods todeliver a desired set dose of therapeutic gas (e.g., NO concentration,mg/kg/hr, NO PPM, etc.) to a patient in need thereof comprising:receiving and/or determining a desired set dose of therapeutic gas to bedelivered to a patient that may be input by a user; measuring flow inthe inspiratory limb of a patient breathing circuit; adjusting a flowcontrol valve to change the amount of therapeutic gas flowing;delivering therapeutic gas containing NO to the patient duringinspiratory flow; monitoring inspiratory flow or changes in theinspiratory flow; and/or varying the quantity (e.g. volume or mass) oftherapeutic gas delivered in a subsequent inspiratory flow.

For another example, the gas analyzing subsystem 180 can perform methodsto determine the concentration of target gas (e.g., NO, CO, etc.) beingdelivered to a patient comprising: actuating a sampling pump and/oropening a gas sampling valve (e.g., three way valve, etc.) to obtain agas sample from the inspiratory limb of a patient breathing circuit, thegas sample being of blended air and therapeutic gas (e.g., NO) beingdelivered to a patient; exposing the gas sample to gas sensors (e.g.,catalytic type electrochemical gas sensors); obtaining information fromthe sensor indicative of the concentration of target gas (e.g., NO,nitrogen dioxide, oxygen) being delivered to the patient; and/orcommunicating to the user the concentration of the target gas. S

For yet another example, the gas analyzing subsystem 180 can performmethod to perform calibrations (e.g., baseline calibrations) of the gassensor (e.g., catalytic type sensor, electrochemical gas sensor, NOsensor, etc.) comprising: actuating a sampling pump and/or opening a gassampling valve (e.g., three way valve, etc.) to obtain a gas sample ofambient air (e.g., conditioned room air); exposing the gas sample ofambient air to gas sensors (e.g., catalytic electrochemical NO gassensors); obtaining information from the sensor indicative ofconcentration of target gas (e.g., NO) in the ambient air (e.g., 0 PPMNO); and/or generating a new calibration line and/or modifying anexisting calibration line by, for example, replacing the initial and/orprevious information indicative of zero concentration target gas (e.g.,0 PPM NO) with the obtained information indicative of zero PPM targetgas and using the slope of the initial and/or previous calibration line(e.g., slope of initial and/or previous calibration line connecting theinitial and/or previous zero and span calibration points). Themachine-executable instructions may also comprise instructions for anyof the other teachings described herein.

In exemplary embodiments, systems and methods of the present inventioncan include one or more gas supply subsystems (e.g., first gas supplysubsystem 110(a), second gas supply subsystem 110(b), etc.) capable ofreceiving therapeutic gas (e.g., from a therapeutic gas source) and/orproviding the therapeutic gas to a primary and/or secondary deliverysubsystem.

First, second gas supply subsystem 110(a), 110(b) can include, but isnot limited to, a receptacle (not shown) for receiving a therapeutic gassource 116(a), 116(b). When received, a therapeutic gas source valve117(a), 117(b) of therapeutic gas source 116(a), 116(b) can be actuatedenabling therapeutic gas to exit from therapeutic gas source 116(a),116(b). In exemplary embodiments, first, second gas supply subsystem110(a), 110(b) can include, but is not limited to, a gas source coupling115(a), 115(b); a gas source connection valve 118(a), 118(b); a gaspressure sensor 120(a), 120(b); a pressure regulator 122(a), 122(b); apurge valve 124(a), 124(b); and/or a shut off 126(a), 126(b). In atleast some instances, a gas source identifier 128(a), 128(b) and/or atemperature sensor 130(a), 130(b) can be affiliated with gas source116(a), 116(b). Further, in at least some instance, a gas sourceidentifier reader 131(a), 131(b); and/or a gas source detector 132(a),132(b); can be used to determine whether or not a gas source has beenreceived and/or loaded properly.

By way of example, gas source coupling 115(a), 115(b) can be configuredto receive therapeutic gas source 116(a), 116(b), enabling a fluid flowconnection with the therapeutic gas source, connection valve 118(a),118(b) with system 100, wherein connection valve 118(a), 118(b) isconfigured to have at least an open state and a closed state. Further,gas pressure sensor 120(a), 120(b) can be adjacent to and in fluidcommunication with connection valve 118(a), 118(b), wherein connectionvalve 118(a), 118(b) provides a gas flow path 119(a), 119(b) from theconnection valve 118(a), 118(b) to gas pressure regulator 122(a),122(b). Following this configuration, the gas pressure sensor can beconfigured to measure a gas pressure at the gas source (e.g., betweenconnection valve 118(a), 118(b) and therapeutic gas pressure regulator122(a), 122(b), for example, at least when the connection valve 118(a),118(b) and therapeutic gas source valve 117(a), 117(b) is in an openstate, etc.). Further, the gas pressure sensor can be configured tomeasure gas pressure at therapeutic gas pressure regulator 122(a),122(b) downstream from gas pressure sensor 120(a), 120(b), connectionvalve 118(a), 118(b). As used herein, “adjacent to” means abutting oradjoining a neighboring component, where an adjacent downstreamcomponent immediately follows the upstream component without otherintervening components, and with minimal internal volume (e.g., deadspace) between the upstream component and the downstream component. Forexample, a connection valve and/or gas pressure sensor may have shortconduits leading to and from the actual mechanisms, so that even if aninlet of a gas pressure sensor were connected directly to an outlet of athe connection valve there may still be a length of fluid flow pathbetween the connection valve mechanism and the gas pressure sensormechanism. Similarly, the fluid flow path may comprise a short length ofconduit 119(a), 119(b) (e.g., tubing, channels, etc.) to which theconnection valve 118(a), 118(b) and the gas pressure sensor 120(a),120(b) may be coupled due to the type of unions used on the gas sourcevalve and the gas pressure sensor. Further, in exemplary embodiments,all conduits placing any and/or all components in fluid connection withtherapeutic gas can be minimized and/or eliminated such that “dead ends”(e.g., dead space between the component and the conduit) can beminimized and/or eliminated, for example, as these “dead ends” can besubstantially difficult to purge and/or can cause NO2 generation and/orNO2 can be substantially difficult to purge from “dead ends”.

While the first gas supply subsystem 110(a) is depicted as being locatedon the left side of the drawing and the second gas supply subsystem110(b) is depicted as being located on the right side of the drawing,this is for illustrative purposes of an exemplary embodiment, and shouldnot be construed as a limitation, for which reference should be made tothe claims. In addition, while the gas supply subsystems may be referredto as a first gas supply subsystem 110(a) and a second gas supplysubsystem 110(b), this is not intended to connote sequence orpreference, but is for ease of reference and should not be construed asa limitation, for which reference should be made to the claims. Further,while the gas supply subsystems may be referred to as a first and secondgas supply subsystems, this should not be construed that there may onlybe two gas supply subsystems as additional gas supply subsystems areenvisioned, rather it is for ease of reference and should not beconstrued as a limitation, for which reference should be made to theclaims.

In various embodiments, the therapeutic gas source 116(a), 116(b) may bea compressed gas cylinder with an initial gas pressure of about 2000 psito about 5000 psi having an NO concentration of about 2000 ppm to about10000 ppm, an initial gas pressure of about 3000 psi having an NOconcentration of about 4880 ppm, an initial gas pressure of about 2000psi to about 5000 psi having an NO concentration of about 400 ppm toabout 1600 ppm, and/or an initial gas pressure of about 1800 psi havingan NO concentration of about 800 ppm. Of course other initial pressuresand/or NO concentrations are envisioned. In one or more embodiments,therapeutic gas source 116(a), 116(b) may be a mini cylinder that cancontain a pressurized therapeutic gas at a pressure in the range ofabout 2000 psi to about 300 psi, or at a pressure of about 3000 psi,where the mini cylinder weighs less than ⅓ the weight of a standardsized gas cylinder (e.g., about 30 lbs. to 50 lbs.) and/or the minicylinder weights about 1.4 lbs. while providing the same or greaterrun-time-to-empty compared to previous cylinders (e.g., standard sizedgas cylinders). In various embodiments, the lighter mini cylinder(s)enables easier manual cylinder distribution because it require lessstrength from a user to move and manipulate, and provides more efficientstorage in a manner that takes up less physical space than largerstandard cylinders. In various embodiments, the mini cylinder maycontain a therapeutic gas having a concentration in the range of about2000 ppm to about 10,000 ppm, or about 4000 ppm to about 10,000 ppm. Invarious embodiments, the therapeutic gas source is an NO mini cylinderhaving an NO concentration of about 2000 ppm to about 10000 ppm, and aninitial gas pressure of about 3000 psi, or an NO concentration of about4880 ppm and an initial gas pressure of about 3000 psi.

In exemplary embodiments, the gas supply system receptacle andtherapeutic gas source can be configured such that only the desiredtherapeutic gas source 116(a), 116(b) can be coupled to the gas supplysubsystem 110(a), 110(b). In at least some instances, to ensure that thedesired gas source is being received, gas source coupling 115(a), 115(b)can be configured to mate with compatible coupling member 114(a), 114(b)of therapeutic gas source 116(a), 116(b). For example, systems andmethods of the present invention can include and/or be modified suchthat they can work with any of the teaching in U.S. Pat. No. 8,757,148entitled “Devices And Methods For Engaging Indexed Valve And PressurizedCanister Assembly With Collar And For Linear Actuation By PlungerAssembly Into Fluid Communication With Device For Regulating DrugDelivery”, the contents of which is incorporated by reference herein inits entirety. In one or more embodiments, the gas source coupling115(a), 115(b) and/or matching coupling member 114(a), 114(b) comprisesan indexed drug delivery device as described in U.S. Pat. No. 8,757,148.Systems and methods of the present invention can include and/or bemodified such that they can work with any of the teaching in U.S. Pat.No. 8,757,148. In various embodiments, the gas source coupling 115(a),115(b) and matching coupling member 114(a), 114(b) are polarized so atherapeutic gas source 116(a), 116(b) may only be coupled with the gassource coupling with a predetermined orientation. In variousembodiments, the therapeutic gas source may be aligned by the gas sourcecoupling, so a gas source identifier 128(a), 128(b) attached to thetherapeutic gas source faces in a particular direction. In at least someinstances, mechanical and visual guides can be used to aid in theloading of the therapeutic gas source into the receptacle.

In various embodiments, gas supply subsystem 110(a), 110(b) may comprisegas source identifier reader 131(a), 131(b) and/or temperature sensor130(a), 130(b) that may be positioned within a bay and/or receptacle forreceiving therapeutic gas source 116(a), 116(b). Gas source identifierreader 131(a), 131(b) and/or temperature sensor 130(a), 130(b) may beused to, amongst other things, obtain data from the gas sourceidentifier 128(a), 128(b), and/or temperature values of the therapeuticgas source 116(a), 116(b). Further, in at least some instance, a gassource detector 132(a), 132(b) can be used to determine whether or not atherapeutic gas source 116(a), 116(b) has been received and/or matedproperly.

In one or more embodiments, therapeutic gas source detector 132(a),132(b) is operatively associated with the gas source coupling 115(a),115(b), where the therapeutic gas source detector 132(a), 132(b) isconfigured to detect when the therapeutic gas source 116(a), 116(b) isproperly received by the respective gas source coupling 115(a), 115(b).In various embodiments, the therapeutic gas source detector 132(a),132(b) is configured to communicate a signal indicating the presence ofthe therapeutic gas source 116(a), 116(b) to the therapeutic gasdelivery system controller and/or respective subsystem controllers129(a), 129(b). In various embodiments, the therapeutic gas sourcedetector 132(a), 132(b) may be for example a micro-switch, a limitswitch, or a proximity detector (e.g., Hall Effect Sensor).

In exemplary embodiments, connection valve 118(a), 118(b) may alsoprevent loud noise or bang from rapid venting of high pressure gas fromconduit/manifold 119 when removing therapeutic gas source 116(a),116(b). Connection valve 118(a), 118(b), in at least some instances, canalso function to keep air out of the high pressure manifold upstream ofpressure regulator 122(a), 122(b).

In exemplary embodiments, pressure regulator 122(a), 122(b) may beconfigured to reduce the high pressure therapeutic gas from thetherapeutic gas source (e.g., 2000 psi, 3000 psi, etc.) to an operatingpressure (e.g., 20 psi, 30 psi, etc.).

In exemplary embodiments, primary gas delivery subsystem 140 can be influid communication with first gas supply subsystem 110(a) and/or secondgas supply subsystem 110(b) such that NO can be received from eitherand/or both gas supply subsystems (e.g., via conduit 101(a), via conduit101(b), etc.). Primary gas delivery subsystem 140 can be in fluidcommunication with a delivery gas pressure sensor(s) 109 (e.g., whichcan be shared between the primary and secondary delivery sub systems asshown) enabling pressure measurement of NO being supplied from eitherand/or both gas supply subsystems and/or the therapeutic gas pressure inconduit 101(a) and conduit 101(b). Further, NO received from eitherand/or both gas supply subsystems can be in fluid communication with afirst primary flow control channel 141(a) (e.g., a high flow controlchannel) and/or a second primary flow control channel 141(b) (e.g., alow flow control channel) such that flow of NO can be controlled. Firstflow control channel 141(a) can be in fluid communication with a firstprimary shut off valve 142(a), a first primary high flow control valve143(a), a first primary delivery flow sensor 146(a), and/or a firstprimary confirmatory flow sensor 148(a). Similarly, second flow controlchannel 141(b) can be in fluid communication with a second primary shutoff valve 142(b), a second primary high flow control valve 143(b), asecond primary delivery flow sensor 146(b), and/or a second primaryconfirmatory flow sensor 148(b).

In exemplary embodiments, gas delivery subsystem 140 can delivertherapeutic gas, at a desired set dose (e.g., a desired concentration)to a patient (e.g., via an injector module coupled to a patientbreathing circuit affiliated with a ventilator). For example, gasdelivery subsystem 140 can wild stream blend therapeutic gas (e.g., NO,etc.), via injector module 107, into patient breathing gas in breathingcircuit 209, affiliated with ventilator 205, as a proportion of thepatient breathing gas. To at least wild stream blend therapeutic gas(e.g. NO, etc.) into patient breathing gas, gas delivery subsystem 140can receive NO from NO gas source 116(a) and/or NO gas source 116(b),via flow control channel 141(a) and/or flow control channel 141(b), andprovide the therapeutic gas, via a delivery conduit 111 that can also bein fluid communication with an injector module 107, which in turn canalso be in fluid communication with the inspiratory limb of breathingcircuit 209 affiliated with ventilator 205. In various embodiments,therapeutic gas flowing through delivery conduit 111 can be the sum oftherapeutic gas flowing through flow control channel 141(a) (e.g., ahigh flow control channel) and flow control channel 141(b) (e.g., a lowflow control channel). Further, to at least wild stream blendtherapeutic gas into patient breathing gas, breathing circuit gas flowinformation can be provided by sensors, such as flow sensor 108(a)and/or flow sensor 108(b) affiliated with injector module 107, in fluidcommunication with the breathing circuit and/or flow information can bereceived from the ventilator.

To regulate flow of NO through delivery conduit 111 to injector module107, and in turn to a patient 203 receiving breathing gas frominspiratory limb 213 of patient breathing circuit 209, one or more flowcontrol valves 143(a) and/or 143(b) (e.g., proportional valves, binaryvalves, etc.) can open enabling NO delivery to patient 203 by flowing NOreceived from at least one of the gas supply subsystems by thecorresponding flow control channel to injector module 107, via deliveryconduit 111, and in turn into inspiratory limb 213 of patient breathingcircuit 209 and to patient 203. In at least some instances, NO deliverysystem 100 can include one or more therapeutic gas flow sensors 146(a),146(b), 148(a), and/or 148(b) that can measure the flow of therapeuticgas through flow control valves 143(a) and/or 143(b) and/or deliveryconduit 111, in turn enabling measurement of the flow of therapeutic gasto injector module 107, and in turn to patient 203

In exemplary embodiments, therapeutic gas flow (e.g., NO gas flow) canbe wild stream blended proportional to the breathing gas (e.g., air)flow to provide a desired set dose concentration of the therapeutic gas(e.g., NO) in the combined breathing gas and therapeutic gas. Forexample, a user can input a desired set dose and the delivery system candeliver this set dose to patient 203. Further, NO delivery system 100can execute, for example, using machine-executable instructions, adelivered concentration calculation that confirms that the desiredconcentration of the therapeutic gas (e.g., NO) is in the combinedbreathing gas and therapeutic gas using the known concentration oftherapeutic gas source 116(a), 116(b); the amount of breathing gas flowin the patient circuit using information from BCG flow sensors 108(a)and/or 108(b) and/or from ventilator 205; and the amount of therapeuticgas flow in delivery conduit 111 going to injector module 107 (and inturn to patient 203) using information from therapeutic gas flow sensors146(a), 146(b), 148(a), and/or 148(b).

With respect to at least the backup, or secondary, delivery subsystem,at times referred to as an “eblender” or the like, of the presentinvention, some found previous backup systems to be difficult andintimidating, and required extensive training with regard to switch overfrom ventilator delivered therapeutic gas to manually deliveredtherapeutic gas. In exemplary embodiments, secondary delivery subsystem160 provides a simple and/or automatic backup system for primarydelivery subsystem 140, as well as a manual ventilation system as asimple and/or automatic backup system for ventilator 205 suppliedbreathing gas and patient breathing circuit 209. Further, in exemplaryembodiments, the present invention provides an automatic backup, orsecondary, delivery system (e.g., eblender), links dose settings of thesecondary delivery subsystem to the dose set at a primary deliverysubsystem so the patient dose remains at the desired set dose, providesmonitoring or confirmation of a set dose, provides backup systems whichcan, if needed, function independently from the rest of the system.

In exemplary embodiments, similar to primary gas delivery subsystem 140,secondary gas delivery subsystem 160 can be in fluid communication withfirst gas supply subsystem 110(a) and/or second gas supply subsystem110(b) such that NO can be received from either and/or both gas supplysubsystems (e.g., via conduit 101(a), via conduit 101(b), via conduit101(a) and conduit 101(b), etc.). Again similar to primary gas deliverysubsystem 140, secondary gas delivery subsystem 160 can be in fluidcommunication a delivery gas pressure sensor(s) 109 (e.g., which can beshared between the primary and secondary delivery subsystems as shown)enabling pressure measurement of NO being supplied from either and/orboth gas supply subsystems. Further, NO received from either and/or bothgas supply subsystems can be in fluid communication with a secondaryflow control channel 161(a) (e.g., a medium flow control channel) suchthat flow of NO can be controlled. Secondary flow control channel 161(a)can be in fluid communication with a secondary shut off valve 162, asecondary medium flow control valve 163, a secondary delivery flowsensor 166, and/or a secondary confirmatory flow sensor 168. Further,secondary flow control channel 161(a) can be in fluid communication witha flow regulating valve 170 that can control whether flow from secondarygas delivery system goes to injector module 107 or to another assistedbreathing apparatus (e.g., a bag valve mask, etc.).

In one or more embodiments, secondary delivery subsystem 160 alsocomprises flow regulating valve 170 that can control whether flow fromsecondary gas delivery system 160 goes to injector module 107 or toanother assisted breathing apparatus (e.g., bag valve mask, etc.). Invarious embodiments, flow regulating valve 170 may be a three-way valvethat is configured to direct a gas flow stream to an injector moduleoutlet or low pressure outlet 167 for a bag valve mask. In variousembodiments, the flow regulating valve 170 may include one or moreproportional control valves, binary valves, or a 3-way valve, where thevalve(s) may be configured to direct the gas flow.

In exemplary embodiments, similar to primary gas delivery subsystem 140,secondary gas delivery subsystem 160 can deliver therapeutic gas, at adesired set dose (e.g., a desired concentration), to a patient (e.g.,via an injector module coupled to a patient breathing circuit affiliatedwith a ventilator). For example, secondary gas delivery subsystem 160can wild stream blend therapeutic gas (e.g., NO, etc.), via injectormodule 107, into patient breathing gas in breathing circuit 209,affiliated with ventilator 205, as a proportion of the patient breathinggas. To at least wild stream blend therapeutic gas (e.g. NO, etc.) intopatient breathing gas, secondary gas delivery subsystem 160 can receiveNO from a NO gas source 116(a) and/or NO gas source 116(b), via flowcontrol channel 161(a) and flow regulating valve 170, and provide thetherapeutic gas, via a delivery conduit 111 that can also be in fluidcommunication with an injector module 107, which in turn can also be influid communication with the inspiratory limb of breathing circuit 209affiliated with ventilator 205. Further, to at least wild stream blendtherapeutic gas into patient breathing gas, breathing circuit gas flowinformation can be provided by sensors, such as flow sensor 108(a)and/or flow sensor 108(b) affiliated with injector module 107, in fluidcommunication with the breathing circuit and/or flow information can bereceived from the ventilator.

To regulate flow of NO through delivery conduit 111 to injector module107, and in turn to a patient 203 receiving breathing gas frominspiratory limb 213 of patient breathing circuit 209, at least one flowcontrol valve 163 (e.g., proportional valves, binary valves, etc.) canopen enabling NO delivery to patient 203 by flowing NO received from atleast one of the gas supply subsystems by the corresponding flow controlchannel to injector module 107, via delivery conduit 111, to injectormodule 107, and in turn into inspiratory limb 213 of patient breathingcircuit 209 and to patient 203. In at least some instances, NO deliverysystem 100 can include one or more therapeutic gas flow sensors 166and/or 168 that can measure the flow of therapeutic gas through the atleast one flow control valve 163 and/or delivery conduit 111, in turnenabling measurement of the flow of therapeutic gas to injector module107, and in turn to patient 203.

In exemplary embodiments, therapeutic gas flow (e.g., NO gas flow) canbe wild stream blended proportional to the breathing gas (e.g., air)flow to provide a desired set dose concentration of the therapeutic gas(e.g., NO) in the combined breathing gas and therapeutic gas. Forexample, a user can input a desired set dose and the delivery system candeliver this set dose to patient 203. Further, NO delivery system 100can execute, for example, using machine-executable instructions, adelivered concentration calculation that confirms that the desiredconcentration of the therapeutic gas (e.g., NO) is in the combinedbreathing gas and therapeutic gas using the known concentration oftherapeutic gas source 116(a), 116(b); the amount of breathing gas flowin the patient circuit using information from BCG flow sensors 108(a)and/or 108(b) and/or from ventilator 205; and the amount of therapeuticgas flow in delivery conduit 111 going to injector module 107 (and inturn to patient 203) using information from therapeutic gas flow sensors166 and/or 168.

In exemplary embodiments, secondary delivery subsystem 160 can receiveoxygen and/or air (e.g., from the low pressure outlet of an external gassupply such as a wall gas regulator, from a wall outlet, cylinder, etc.)that can be wild stream blended with NO, for example, from gas supplysubsystem A and/or gas supply subsystem B as described above, which inturn can be delivered to an assisted breathing apparatus (e.g., a bagvalve mask). By way of example, to at least wild stream blend NO withoxygen and/or air (e.g., from the low pressure outlet of a wall gasregulator, from a wall outlet, etc.) NO received from either and/or bothgas supply subsystems can be in fluid communication with secondary flowcontrol channel 161(a) (e.g., a medium flow control channel) such thatflow of NO can be controlled. Further, a low pressure conduit 172 canreceive low pressure oxygen and/or air (e.g., from the low pressureoutlet of a wall gas regulator) via low pressure conduit pass throughinlet (e.g., coupled to a low pressure delivery conduit from the lowpressure outlet of a wall gas regulator), that may be in fluidcommunication with a filter, and this received low pressure air can bewild stream blended with NO from either and/or both gas supplysubsystems, for example at blending junction 169. Low pressure conduit172 can be in fluid communication with a low pressure oxygen/airreceived flow sensor 174, a low pressure oxygen/air receivedconfirmatory flow sensor 176, and/or a low pressure oxygen/air receivedpressure sensor 178. Following the above example, flow regulating valve170 (e.g., a three way valve, directional valve, etc.) can be actuatedsuch that NO from secondary flow control channel 161(a) flows toblending junction 169 wherein the NO and oxygen and/or air can be wildstream blended, and in turn, this NO and air and/or oxygen can flow tothe assisted breathing apparatus (e.g., a bag valve mask, etc.).

For ease, in at least this configuration, the assisted breathingapparatus is, at times, described as a bag valve mask. Of course otherassisted breathing apparatus are envisioned such as, but not limited to,a bag valve mask, nasal cannula, face mask, etc. Accordingly, referenceto a bag valve mask is merely for ease and is in no way meant to be alimitation.

In exemplary embodiments, secondary gas delivery subsystem 160 candeliver therapeutic gas, at a desired set dose (e.g., a desiredconcentration), to a patient, via a bag valve mask, by wild streamblending therapeutic gas (e.g., NO, NO from either and/or both gassupply subsystems, etc.) into low pressure oxygen and/or air (e.g., fromthe low pressure outlet of a wall gas regulator) as a proportion of lowpressure oxygen and/or air. Further, to at least wild stream blendtherapeutic gas into low pressure oxygen and/or air, flow informationcan be provided by sensors, such as flow sensor 174, flow sensor 176,and/or pressure sensor 178, in fluid communication low pressure conduit172. For ease, only a low pressure oxygen and/or air/O2 is described.This is merely for ease and is in no way meant to be a limitation, forexample, as usage of high pressure oxygen and/or air is envisioned. Forexample, conduits, valves, flow sensors, etc. can be modified for highpressure and/or therapeutic gas delivery system 100 can include and/orfunction with a pressure regulator (e.g., to decrease the sourcepressure, etc.). Accordingly, one skilled in the art will appreciate howtherapeutic gas system 100 may function with high pressure oxygen and/orair.

As described above with respect to NO delivery to injector module 107,to regulate flow of NO through flow control channel 161(a) to a bagvalve mask, and in turn to a patient 203, at least one flow controlvalve 163 (e.g., proportional valves, binary valves, etc.) can openenabling NO flow to blending junction 169. At blending junction 169 NOand low pressure oxygen and/or air can be wild stream blended and thisNO and oxygen and/or air can in turn flow to a bag valve mask. In atleast some instances, NO delivery system 100 can include one or moretherapeutic gas flow sensors 166 and/or 168 that can measure the flow oftherapeutic gas through the at least one flow control valve 163 and/orflow control channel 161(a), in turn enabling measurement of the flow oftherapeutic gas to blending junction 169.

In exemplary embodiments, therapeutic gas flow (e.g., NO gas flow) canbe wild stream blended proportional to the low pressure oxygen and/orair flow to provide a desired set dose concentration of the therapeuticgas (e.g., NO) in the combined low pressure oxygen and/or air andtherapeutic gas. For example, a user can input a desired set dose andthe delivery system 160 can deliver this set dose to patient 203.Further, NO gas delivery system 100 can execute, for example, usingmachine-executable instructions, a delivered concentration calculationthat confirms that the desired concentration of the therapeutic gas(e.g., NO) is in the combined low pressure oxygen and/or air andtherapeutic gas using the known concentration of therapeutic gas source203; the amount of low pressure oxygen and/or air using information fromflow sensors 174 and/or 176; and the amount of therapeutic gas flow fromflow control channel 161 going to blending junction 169 usinginformation from therapeutic gas flow sensors 166 and/or 168.

In exemplary embodiments, overpressure valve 179 can be in fluidcommunication with low pressure conduit 172 to, for example, ensure thatthe pressure in low pressure conduit 172 is not above a predeterminedthreshold. Overpressure valve 179 can be used to ensure that sensors influid communication with low pressure conduit 172 and/or low pressureconduit 172 itself is not damaged by being exposed to high pressure gas(e.g., that may be provided from the high pressure outlet of an oxygenand/or air source).

In at least some instances, system 100 can have fewer or additionaldelivery subsystems (e.g., primary delivery subsystem 140, secondarydelivery subsystem 160, etc.) and/or system 100 and/or deliverysubsystems can have fewer or additional flow control channels andassociated elements. For ease, only a primary delivery subsystem havingtwo flow control channels and associated elements (e.g., shut offvalves, control valves, flow sensors, confirmatory flow sensors, etc.)and a secondary delivery subsystem having a single flow control channelsand associated elements (e.g., shut off valves, control valves, flowsensors, confirmatory flow sensors, etc.) are shown. This is merely forease and is in no way meant to be a limitation. For example, primarydelivery subsystem can include any number of flow control channels, suchas, a third flow control channel (not shown) that may be in fluidcommunication with associated elements (e.g., a third primary shut offvalve, a third primary flow control valve, a third primary delivery flowsensor, and/or a third primary confirmatory flow sensor, etc.). Foranother example, secondary delivery subsystem can include any number offlow control channels, such as, a second flow control channel (notshown) that may be in fluid communication with associated elements(e.g., a second secondary shut off valve, a second secondary flowcontrol valve, a second secondary delivery flow sensor, and/or a secondsecondary confirmatory flow sensor, etc.). For yet another example,system 100 can include a tertiary delivery subsystem (not shown) thatcan have any number of flow control channels, such as, a first flowcontrol channel that may be in fluid communication with associatedelements (e.g., a first tertiary shut off valve, a first tertiary flowcontrol valve, a first tertiary delivery flow sensor, and/or a firsttertiary confirmatory flow sensor, etc.), a second flow control channelthat may be in fluid communication with associated elements (e.g., asecond tertiary shut off valve, a second tertiary flow control valve, asecond tertiary delivery flow sensor, and/or a second tertiaryconfirmatory flow sensor, etc.), and/or a third flow control channelthat may be in fluid communication with associated elements (e.g., athird tertiary shut off valve, a third tertiary flow control valve, athird tertiary delivery flow sensor, and/or a third tertiaryconfirmatory flow sensor, etc.).

In at least some instances, flow control valves can control variousranges of flow (e.g., high flow, low flow, medium flow, etc.) and/or thesame range of flows (e.g., one or more high flow valves, one or more lowflow valves, one or more medium flow valves, etc.). For ease, flowcontrol valves (e.g., flow control valve 143(a), flow control valve143(b), flow control valve 163, etc.) are, at times, described as highflow control valves, low flow control valves, medium flow controlvalves, and the like. This is merely for ease and is in no way meant tobe a limitation. Of course other ranges of flow and/or additional flowcontrol valves and/or ranges are envisioned.

In at least some instances, flow control valves (e.g., flow controlvalve 143(a), flow control valve 143(b), flow control valve 163, etc.)can be any type of valve capable of controlling gas flow such as, butnot limited to, proportional valves, binary valves, any combination orfurther separation thereof, and/or any other type of valve.

In at least some instances, therapeutic gas flow sensors 146(a), 146(b),148(a), 148(b), 166, and/or 168 and flow control valves (e.g., flowcontrol valve 143(a), flow control valve 143(b), flow control valve 163,etc.) in corresponding flow control channels can be configured such thatthe flow sensors may be upstream, downstream, and/or combinationsthereof of the corresponding flow control valve(s). Therapeutic gasdelivery system 100 is described, at times, as having flow sensors onecorresponding confirmatory flow sensor. This is merely for ease and isin no way meant to be a limitation because, for example, more than onecorresponding confirmatory flow sensor is envisioned.

In one or more embodiments, the therapeutic gas delivery system 100 canhave one or more inlet ports and outlet ports, where the ports may begeneral ports to allow connecting and/or fluid communication of thesystem to external components (e.g., injector module outlet port), ordedicated ports that provide connection and/or fluid communication ofexternal components to particular subsystem(s) and/or components toprovide specific system functions (e.g., low pressure air inlet port,gas analyzing inlet port). In various embodiments, the inlet ports andoutlet ports may comprise connectors, for example quick disconnect gasconnectors, hose barb connectors, and hose couplings, to name a few. Inexemplary embodiments, therapeutic gas delivery system 100 can comprisea primary outlet port (also referred to as an injector module outletport) for connection to an injector module, a low pressure outlet 167for connection to a manual ventilation device, and a low pressure inletport 165 for connection to a low pressure air/O.sub.2 supply.

In exemplary embodiments, therapeutic gas delivery system 100 can allowa user to input a desired set dose of the therapeutic gas (e.g., NO inPPM) and the therapeutic gas delivery system can confirm that thedesired set dose of the therapeutic gas is being delivered to thepatient by calculating the delivery concentration (e.g., as describedabove) as well as using gas analyzing system 180 to confirm the desiredset dose of the therapeutic gas (e.g., NO) is being delivered to thepatient. Gas analyzing subsystem 180 can include, but is not limited tonumerous sensors such as, but not limited to, an electrochemical NO gassensor 182, which may have a catalytic type electrode material with highcatalytic activity for the electrochemical reactions of the sensor, acatalytic type electrochemical nitrogen dioxide gas sensor 186, and agalvanic type electrochemical oxygen gas sensor 188, to name a few; asample gas flow sensor(s) 190; a sample pump(s) 192; sample systemvalve(s) 194; and/or controller 184. Sensors 182, 186, and 188 can be inseries and/or parallel and/or can be in any order. For ease, sensors182, 186, and 188 are illustratively depicted as being in series. Thisis merely for ease and is in no way meant to be a limitation. In variousembodiments, the NO sensor may be an electrochemical sensor, which maycomprise two electrodes, including a sensing and a counter electrode,separated by a thin layer of electrolyte.

In exemplary embodiments, gas analyzing subsystem 180 can sample and/ormeasure the concentration of various gases being delivered to a patient.The concentration of NO being delivered to patient 203 can be sampledand exposed to NO sensor 182, which in turn can output informationindicative of the concentration of NO in the breathing gas (e.g., NOPPM). For example, a sample of the gas being delivered to the patientcan be sampled via a sample line 119 that is in fluid communication withinspiratory line 213 of breathing circuit 209 affiliated with breathingapparatus 205. Sample line 119 can be in fluid communication withinspiratory limb 213 via a sampling “T” 121 which can be coupled toinspiratory line 213. This gas sample from the inspiratory limb, viasample line 119, can flow and/or be pulled to the gas sensors 182, 186,188 (e.g., NO sensor 182, nitrogen dioxide gas sensor 186, oxygen gassensor 188, etc.). Flow in sample line 119 can be regulated via valve194 and/or sample pump 192. Sample line mass or volume flow can bemeasured using flow sensor 190. Sample line 119 can also be in fluidcommunication with a gas sample conditioner 196 that may condition thesample gas, for example, by extracting fluids, placing the sample at theappropriate humidity, removing contaminants from the sample, and/or cancondition the sample gas in any other way as desired.

In exemplary embodiments, gas analyzing subsystem 180 can performcalibrations (e.g., baseline calibrations, span calibrations, etc.) ofthe gas sensor (e.g., catalytic type electrochemical gas sensor, etc.)by sampling and/or measuring the concentration of target gases in acontrolled sample (e.g., baseline sample, span sample, etc.), where aspan sample is a target gas (i.e., nitric oxide) with a specific knownand controlled concentration within a range of interest (e.g., 10 PPM,25 PPM, 50 PPM, 80 PPM, etc.) and/or where a baseline sample is a gascontaining zero concentration of a target gas (i.e., conditioned ambientair containing zero nitric oxide). For example, a sample of ambient gasand/or span gas can be sampled via a sample line 119 and/or 198 that canbe in fluid communication with valve 194. This gas sample can flowand/or be pulled to the gas sensors (e.g., NO sensor 182, etc.) whereinthe flow can regulated via valve 194 (e.g., a three way valve, etc.)and/or sample pump 192. Sample line flow can be measured using flowsensor 190.

In exemplary embodiments, sample line 119 can also be in fluidcommunication with a gas sample conditioner (not shown) that maycondition the sample gas, for example, by extracting fluids, placing thesample at the appropriate humidity, removing contaminants from thesample, and/or can condition the sample gas in any other way as desired.For example, the ambient air used for the baseline calibration may bescrubbed of any undesirable gases using a scrubber material. By way ofexample, this scrubbing material can be an inline Potassium permanganatescrubber material capable of scrubbing the ambient air removing NO andNO2. With the NO and NO2 removed from the ambient air, the scrubbed aircan be used for a zero calibration as these undesirable gases have beenremoved hence they are at 0 PPM. If needed, a similar technique (e.g.,using an inline scrubber material) can be done for span gas.

Therapeutic Gas Source Management

In exemplary embodiments, at least some aspect of the present inventionrelate to systems, methods, and/or process for, amongst other things,managing use of one or more therapeutic gas sources, receipt oftherapeutic gas source, receiving information from therapeutic gassources, performing run-time-to-empty calculations, providinginformation pertaining run-time-to-empty to users, and/or providingalarms, to name a few.

In one or more embodiments, therapeutic gas source 116(a), 116(b) can bereceived by receptacle/gas supply subsystem 110(a), 110(b). To bereceived by receptacle/gas supply subsystem 110(a), 110(b), couplingmember 114(a), 114(b) of therapeutic gas source 116(a), 116(b) may berequired to mate with gas source coupling 115(a), 115(b) ofreceptacle/gas supply subsystem 110(a), 110(b). After being received,therapeutic gas source 116(a), 116(b) can be actuated (opened) therebyplacing therapeutic gas source 116(a), 116(b) in fluid communicationwith gas pressure sensor 120(a), 120(b), which measures the pressure ofthe gas in therapeutic gas source 116(a), 116(b).

In exemplary embodiments, when received by therapeutic gas deliverysystem 100, gas source identifier reader 131(a), 131(b) can read gassource identifier 128(a), 128(b), which has recorded thereon the actualmeasured concentration of the therapeutic gas in gas source 116(a),116(b) and/or the manufacturer's target gas concentration fortherapeutic gas source 116(a), 116(b). Gas source identifier 128(a),128(b) may also have recorded thereon additional data such as, but notlimited to, the wetted volume of the gas source, the identity of thetherapeutic gas, and/or its expiration date, to name a few. Datarecorded on gas source identifier 128(a), 128(b) and gas pressuremeasured by gas pressure sensor 120(a), 120(b) can be communicated totherapeutic gas delivery system controller and stored in memory. Inexemplary embodiments, at least some of the information recorded on gassource identifier 128(a), 128(b) can be used for run-time-to-emptycalculations.

In one or more embodiments, gas source identifier 128(a), 128(b) may beradio-frequency identification (RFID) tags with read/write (R/VV) memoryin the communicating component, used to transmit data to the systemcontroller(s) via an RFID reader 131(a), 131(b), bar codes and/or QRcodes.

In various embodiments, gas source identifier reader 131(a), 131(b) maybe an imaging device (e.g., camera) for reading and communicating actualgas concentration data on a QR code, or a barcode scanner for readingand communicating actual gas concentration data on a barcode. In one ormore embodiments, gas source identifier reader 131(a), 131(b) may be acomponent of the bay or receptacle for the engagement of the therapeuticgas source in the therapeutic gas supply subsystem 110(a), 110(b). Thebay or receptacle may further include means for correctly aligning thegas source within the bay or receptacle for reading the actual therapygas concentration data. Corresponding means for aligning may beincorporated in the therapy gas source via imaging camera, or an RFIDreader for reading and communicating actual gas concentration data on anRFID tag, where the tag may be unreadable if facing in the wrongdirection. In certain embodiments, the means for aligning may include akeying arrangement between the gas source (e.g., via the gas sourcevalve body) and the bay or receptacle receiver, or markings on the bayor receptacle and the gas source to be aligned upon placement of the gassource into the therapeutic gas delivery system. Such means for gassource alignment may also be used to prevent attachment of an incorrectgas source to the therapy gas delivery system.

In one or more embodiments, shut off valve 126(a), 126(b), which may belocated downstream from and in fluid communication with the purge valve124(a), 124(b), can provide a gas barrier between the gas supplysubsystem 110(a), 110(b) and the primary delivery subsystem 140 and/orsecondary delivery subsystem 160, and may block gas flow to therapeuticgas conduit(s) 101(a), 101(b). Shut off valve(s) 126(a), 126(b) may bebinary valve(s). In one or more embodiments, a therapeutic gas conduit101(a), 101(b) may provide a gas flow path (e.g., an enclosed gas flowpath, tubing, channel, etc.) at least from the at least one gas supplysubsystem to at least one primary gas delivery subsystem (e.g., primarydelivery subsystem 140, etc.) and/or the at least one secondary gasdelivery subsystem (e.g., secondary delivery subsystem 160).

In various embodiments, gas conduit pressure sensor 109 is connected toand in fluid communication with therapeutic gas conduit(s) 101(a),101(b), is configured to measure a gas pressure in therapeutic gasconduit(s) 101(a), 101(b) being delivered to primary delivery subsystem140 and/or secondary delivery subsystem 160, and/or is configured to bein communication, via a communication path, with a therapeutic gasdelivery system controller. In various embodiments, gas pressure sensor120(a), 120(b) is on the high pressure side (e.g., 3000 psi) oftherapeutic gas pressure regulator 122(a), 122(b), while gas conduitpressure sensor 109 is on the regulated/downstream pressure side (e.g.,30 psi) of therapeutic gas pressure regulator 122(a), 122(b).

In one or more embodiments, with therapeutic gas source 116(a), 116(b)received by system 100, NO can be provided from either and/or both gassupply subsystem 110(a), 110(b) and, in turn, be fluidly communicatedwith first flow control channel 141(a) (e.g., a high flow controlchannel) and/or second flow control channel 141(b) (e.g., a low flowcontrol channel) such that flow of the therapeutic gas (e.g., NO) can becontrolled. In various embodiments, a high flow control channel may beconfigured to supply higher flow rates and thereby higher doses moreaccurately, whereas a low flow control channel may be configured tosupply lower flow rates and thereby lower doses more accurately.

In exemplary embodiments, system 100 can automatically activate whendose set and injector module flow (e.g., inspiratory flow, forward flow,etc.) are above a pre-determined threshold, which would be flow ratesindicative of an operational ventilator. By way of example, primarydelivery subsystem 140 and/or secondary delivery subsystem 160 canautomatically activate when dose set and injector module flow aredetermined to be above a pre-determined threshold. This can beaccomplished, because, as noted above, the therapeutic gas deliverysystem controller (e.g., primary gas delivery subsystem controller 144and/or secondary gas delivery subsystem controller 164, etc.) can beconfigured to communicate with first, second primary shut off valve142(a), 142(b); first, second primary flow control valve 143(a), 143(b);first, second primary delivery flow sensor 146(a), 146(b); first, secondprimary confirmatory flow sensor 148(a), 148(b); secondary shut offvalve 162, secondary medium flow control valve 163, secondary deliveryflow sensor 166, and/or secondary confirmatory flow sensor 168, flowregulating valve 170, injector module delivery flow sensor 108(a),and/or injector module confirmatory flow sensor 108(b). In at least someinstances, the first, second primary shut off valve 142(a), 142(b);first, second primary flow control valve 143(a), 143(b); first secondaryshut-off valve 162, and first secondary flow control valve 163 arenormally closed.

In various embodiments, primary delivery subsystem controller 144 maycompare flow rate values received from first primary delivery flowsensor 146(a) and first primary confirmatory flow sensor 148(a) for thetherapeutic gas, and may provide an alarm, recommend replacing at leastone of the sensors, perform verification processes (described below ingreater detail) to confirm which sensor is not functioning properly,and/or provide flow information from the functioning flow sensor, etc.if therapeutic gas flow rates measured at first primary delivery flowsensor 146(a) and first primary confirmatory flow sensor 148(a) differfrom each other by greater than a threshold amount of about 10%, orabout 7%, or about 5%, or about 2.5%, or about 2%, or about 1%, or about0.5%.

In various embodiments, primary delivery subsystem controller 144 maycompare flow rate values received from second primary delivery flowsensor 146(b) and second primary confirmatory flow sensor 148(b) for thetherapeutic gas, and may provide an alarm, recommend replacing at leastone of the sensors, perform verification processes (described below ingreater detail) to confirm which sensor is not functioning properly,and/or provide flow information from the functioning flow sensor, etc.if therapeutic gas flow rates measured at second primary delivery flowsensor 146(b) and second primary confirmatory flow sensor 148(b) differfrom each other by greater than a threshold amount of about 10%, orabout 7%, or about 5%, or about 2.5%, or about 2%, or about 1%, or about0.5%.

In exemplary embodiments, the arrangement of first, second primarydelivery flow sensor 146(a), 146(b) and/or first, second primaryconfirmatory flow sensor 148(a), 148(b) provides monitoring of theprimary delivery subsystem that may consist of at least 3 sets ofsensors for triangulation of failure, including injector module deliveryflow sensor 108(a) and/or injector module confirmatory flow sensor108(b), first, second primary delivery flow sensor 146(a), 146(b) and/orfirst, second primary confirmatory flow sensor 148(a), 148(b), andtherapeutic gas sensor 182, where flow rate values from the flow sensorscan be compared, ratio-metric calculations be performed and compared tothe therapeutic gas sensor value to determine if any of these componentshave failed, or need service and/or calibration. Further, in at leastsome instances, therapeutic gas delivery system 100 can automaticallyperform verification processes (e.g., triangulation of failure, etc.)during delivery of therapeutic gas to a patient and/or if therapeuticgas sensor identifies a failed sensor, valve, or other component isidentified then therapeutic gas delivery system 100 can use informationfrom another sensor, valve, or other component that is functioning. Byway of example, during delivery of therapeutic gas to a patient,therapeutic gas delivery system 100 can perform verification processes(e.g., triangulation of failure) and identify that a flow sensor is notfunctioning and therefor use flow information from a confirmatory flowsensors. Similar calculation and comparisons are described for a pre-useperformance verification described herein.

Secondary Delivery Subsystem

In exemplary embodiments, at least some aspect of the present inventionrelate to systems, methods, and/or process for, amongst other things,providing therapeutic gas from one or more sources, providingtherapeutic gas from a primary delivery subsystem, providing therapeuticgas from a secondary delivery subsystem, providing therapeutic gas froma primary and secondary delivery subsystem, providing therapeutic gas toa ventilated patient, and/or providing therapeutic gas to an assistedbreathing apparatus, to name a few.

In exemplary embodiments, as described above, therapeutic gas deliverysystem 100 can include a plurality of delivery subsystems capable ofreceiving therapeutic gas from a plurality of sources and deliver thereceived therapeutic gas to a patient in need thereof using varioustechniques (e.g., delivery to injector module from primary deliverysubsystem, delivery to injector module from secondary deliverysubsystem, delivery to injector module from primary delivery subsystemand secondary delivery subsystem, delivery to an external manualventilation device from secondary delivery subsystem, delivery to anexternal manual ventilation device from primary delivery subsystem,etc.). To accomplish at least the above, therapeutic gas delivery system100 can include primary delivery subsystem 140, which may comprise twoflow control channels and secondary delivery subsystem 160, which maycomprise a secondary flow control channel, such that a therapeutic gasdelivery system 100 comprises three redundant flow control channels influid communication with therapeutic gas conduit(s) 101(a), 101(b).

In exemplary embodiments, NO received from either and/or both gas supplysubsystems can be in fluid communication with a secondary flow controlchannel 161(a) (e.g., a medium flow control channel) such that flow ofNO can be controlled. Secondary flow control channel 161(a) can be influid communication with a secondary shut off valve 162, a secondarymedium flow control valve 163, a secondary delivery flow sensor 166,and/or a secondary confirmatory flow sensor 168. Further, secondary flowcontrol channel 161(a) can be in fluid communication with a flowregulating valve 170, which may be a 3-way valve that can controlwhether flow from the secondary gas delivery system 160 goes to injectormodule 107 or to outlet port 167 to another external manual ventilationdevice (e.g., bag valve mask). In various embodiments, secondarydelivery subsystem 160 may have its own purge valve in fluidcommunication with flow control channel 161(a).

In exemplary embodiments, flow regulating valve 170 may be oriented(e.g., in reverse), so that at least one of the flow controllers in theprimary gas delivery subsystem can back up the flow controller insecondary system. In various embodiments, flow regulating valve 170 canswitch from being closed or delivering a therapeutic gas to the lowpressure outlet 167 to delivering the therapeutic gas to the primaryoutlet and therapeutic gas delivery line 111 at the same dose as wasbeing delivered by primary delivery subsystem 140.

In exemplary embodiments, the secondary delivery subsystem controller,primary delivery subsystem controller, and/or the system controller maydetect problems (e.g. loss of communication with primary system) and, inat least some instances, respond to the detected problem. For example,delivery subsystem controller(s) 144 and/or 164 may detect a failure inone or more of the flow control channels of primary gas delivery system140, automatically switch therapeutic gas flow control to a flow controlchannel of secondary delivery subsystem 160, and switch flow regulatingvalve 170 to deliver the therapeutic gas to primary outlet 172 and, inturn, to therapeutic gas delivery line 111. For another example,delivery subsystem controller(s) 144 and/or 164 may detect a failure inone of the two flow control channels of primary gas delivery system 140and automatically switch from the failed therapeutic gas flow control tothe other functioning flow control channel of primary gas deliverysystem 140 and/or change the flow of the functioning flow controlchannel to provide the desired set dose. Using at least the abovetechnique the patient can be able stay on the ventilator with deliveryat the same dose setting. For example, since the therapeutic gas isstill delivered to therapeutic gas delivery line 111 and injector module107, the gas analyzing subsystem still detects the amount of therapeuticgas being delivered by secondary delivery subsystem 160, and can displaythe amount to a user to allow continued monitoring of the delivereddose.

In various embodiments, secondary delivery subsystem 160 may have itsown internal battery backup (not shown) separate from the main systembattery (not shown). In various embodiments, two or more batteries maybe able to power primary delivery subsystem 140 and secondary deliverysubsystem 160, so in the event of a battery failure the other can beavailable.

In one or more embodiments, secondary delivery subsystem controller 164and/or system controller may be configured to perform ratio-metric flowcalculations for the concentration of therapeutic gas being delivered tothe patient 203 based on the values from secondary delivery flow sensor166 and/or secondary confirmatory flow sensor 168, and from injectormodule delivery flow sensor 108(a) and/or injector module confirmatoryflow sensor 108(b), which measure ventilation flow rate in the breathingcircuit or nasal cannula passing through the injector module. Inexemplary embodiments, secondary delivery flow sensor 166 and/orsecondary confirmatory flow sensor 168 provides monitoring of thesecondary delivery subsystem that may consist of 3 sets of sensors fortriangulation of failure, including injector module delivery flow sensor108(a) and/or injector module confirmatory flow sensor 108(b), secondarydelivery flow sensor 166 and/or secondary confirmatory flow sensor 168,and therapeutic gas sensor 182, where flow rate values from the flowsensors can be compared, the ratio-metric calculations done and comparedto the therapeutic gas sensor value to determine if any of thesecomponents have failed.

In various embodiments, secondary delivery subsystem controller 164 maycompare flow rate values received from secondary delivery flow sensor166 and secondary confirmatory flow sensor 168 for therapeutic gas, andmay provide an alarm, recommend replacing at least one of the sensors,perform verification processes (described below in greater detail) toconfirm which sensor is not functioning properly, and/or provide flowinformation from the functioning flow sensor, etc. if the therapeuticgas flow rates measured at the secondary delivery flow sensor 166 andthe secondary confirmatory flow sensor 168 differ from each other bygreater than a threshold amount of about 10%, or about 7%, or about 5% ,or about 2.5%, or about 2%, or about 1%, or about 0.5%.

In one or more embodiments, as described above, secondary gas deliverysubsystem 160 also comprises two or more flow sensors 176, 174 along thegas flow path between the flow regulating valve 170 and a low pressureinlet port 165, where the two or more flow sensors 174, 176 are in fluidcommunication with each other and are located relative to each other inseries, parallel, skewed, and/or any other configuration; pressuresensor 178 in fluid communication with the two or more flow sensors 174,176, and/or low pressure outlet port 167. Further, the gas flow pathfrom the inlet may intersect the gas flow path from the flow regulatingvalve 170 at blending junction 169. In various embodiments, secondarydelivery flow sensor 166, and secondary confirmatory flow sensor 168 arein fluid communication with each other and are located relative to eachother in series, parallel, skewed, and/or any other configuration.

In exemplary embodiments, secondary delivery subsystem 160 canautomatically activate and/or deactivate when air/O2 flow (e.g., lowpressure air/O2 from a wall outlet, from a compressor, etc.) is above apredetermined threshold and/or below a predetermined threshold. Forexample, if flow sensor(s) 176, 174 detect air/O2 flow rates greaterthan pre-set threshold (e.g. 0.5 SLPM for 2 seconds, flow ratesindicative of wall flow, etc.) then secondary flow control valve 163 canautomatically activate to deliver the set dose. Further, if flowsensor(s) 176, 174 detect air/O2 flow rates lower than pre-set threshold(e.g. 0 flow for 2 seconds) then secondary flow control valve 163 canautomatically deactivate. Using at least the above, secondary deliverysubsystem 160 can automatically activate and/or deactivate when a user(e.g., nurse, doctor, etc.) turns on and/or off air/O2 flow. In at leastsome instances, therapeutic gas delivery system 100, may alert the userof deactivation of NO delivery, for example, in case Air/O2 wasmistakenly turned off and/or in case the low pressure tubing becamedisconnected from the secondary delivery system. Further, in exemplaryembodiments, when flow is detected a prompt may be provided for the userto squeeze the bag valve mask a multiple times to perform a purge of thebag valve mask.

In exemplary embodiments, secondary delivery subsystem 160 can detectwhen and/or activate in response to squeezing of a valve mask bag. Forexample, manual activation may prompt the user to start air/O2 flow atwall flowmeter and may trigger a prompt to squeeze the bag valve maskmultiple times to purge NO.sub.2 (e.g., that may be generated as NOdelivery can begin automatically in response to air/O2 flow detection,etc.) During each squeeze of the bag valve mask flow rates may bedetected above a pre-set threshold (e.g., change in flow indicative ofsqueezing the bag valve mask) and secondary flow control valve 163 canautomatically activate to deliver the set dose. Similarly, when nosqueeze of the bag valve mask is detected (e.g., flow rates below apre-set threshold indicative of no squeezing of the bag valve mask),then secondary flow control valve 163 can automatically deactivate tohalt deliver of the set dose.

In exemplary embodiments, secondary delivery subsystem 140 can detectwhen a user (e.g., nurse, doctor, etc.) attached air/O2 flow (e.g., lowpressure air/O2 from a wall outlet, from a compressor, etc.)incorrectly, for example, such that the bag valve mask is coupled to theinlet port rather than the outlet port and/or the air/O2 flow is coupledto the outlet port 167 rather than the inlet port 165 and, in at leastsome instances, provide an alert. For example, secondary delivery flowsensor 166, secondary confirmatory flow sensor 168, low pressure flowsensor 174, and/or low pressure confirmatory flow sensor 176 (e.g.,bi-directional flow sensors) can detect air/O2 flow in reverse (e.g.hooked up backwards) and may provide an alarm if reverse flow isdetected.

In exemplary embodiments, when the dose is set to 0, secondary gasdelivery subsystem 160 can still automatically activate upon detectionof activation conditions (e.g., such as those described above) anddeliver default dose of 20 ppm NO when a system dose may be set to 0. Invarious embodiments, secondary gas delivery subsystem 160 dose may beset to a different dose than for the primary gas delivery subsystem 140,where a user may input separate doses for the primary gas deliverysubsystem 140 and the secondary gas delivery subsystem 160. In variousembodiments, secondary gas delivery subsystem 160 can detect elevatedhumidity or changes in gas density and compensate and/or provide analarm.

In one or more embodiments, flow sensor 174 may be a low pressuredelivery flow sensor and flow sensor 176 may be a low pressureconfirmatory flow sensor. In various embodiments, secondary deliverysubsystem controller 164 may compare the flow rate values received fromlow pressure delivery flow sensor 174 and low pressure confirmatory flowsensor 176 for the low pressure breathing gas, and may provide an alarm,recommend replacing at least one of the sensors, perform verificationprocesses (described below in greater detail) to confirm which sensor isnot functioning properly, and/or provide flow information from thefunctioning flow sensor, etc. if the breathing gas flow rates measuredat the low pressure confirmatory flow sensor 176, and the low pressuredelivery flow sensor 174 differ from each other by greater than athreshold amount of about 10%, or about 7%, or about 5%, or about 2.5%,or about 2%, or about 1%, or about 0.5%.

In exemplary embodiments, secondary delivery subsystem 160 can receiveoxygen and/or air from a low pressure gas supply (e.g., from the lowpressure outlet of a wall gas regulator, from a wall outlet, etc.) thatcan be wild stream blended with NO, for example, from gas supplysubsystem A 110(a) and/or gas supply subsystem B 110(b) as describedabove, which in turn can be delivered to an assisted breathing apparatus(e.g., bag valve mask). In various embodiments, the low pressure gassupply may be a wall supply and/or a pressurized cylinder configured toprovide air, oxygen, or a combination thereof. By way of example, to atleast wild stream blend NO with oxygen and/or air (e.g., from the lowpressure outlet of a wall gas regulator, from a wall outlet, etc.) NOreceived from either and/or both gas supply subsystems can be in fluidcommunication with secondary flow control channel 161(a) (e.g., a mediumflow control channel) such that flow of NO can be controlled. Further,low pressure conduit 172 can receive low pressure oxygen and/or air(e.g., from the low pressure outlet of a wall gas regulator) via lowpressure conduit pass through inlet port (e.g., coupled to a lowpressure delivery conduit from the low pressure outlet of a wall gasregulator) and this received low pressure air can be wild stream blendedwith NO from either and/or both gas supply subsystems, for example atblending junction 169. Blending junction 169 may be configured to mix atherapeutic gas delivered by flow control channel 161(a) with a gasreceived at least one of the one or more inlet ports. Low pressureconduit 172 can be in fluid communication with low pressure oxygen/airreceived flow sensor 174, low pressure oxygen/air received confirmatoryflow sensor 176, and/or low pressure oxygen/air received pressure sensor178. Following the above example, flow regulating valve 170 can beactuated such that NO from secondary flow control channel 161 flows toblending junction 169 wherein the NO and oxygen and/or air can be wildstream blended, and in turn, this NO and air and/or oxygen can flow tothe assisted breathing apparatus (e.g., bag valve mask, nasal cannula,etc.). In exemplary embodiments, a pressure relief valve 179 can be influid communication with low pressure conduit 172 to, for example,ensure that the pressure in low pressure conduit 172 is not above apredetermined threshold. In various embodiments, secondary deliverysubsystem controller 164 may detect when pressure sensor 178 measures apressure above or below a predetermined range, which may indicate a highpressure gas source has been attached to low pressure inlet port 165, oran assisted breathing apparatus (e.g., bag valve mask) has becomedisconnected from low pressure outlet port 167. Alarms may be providedwhen secondary delivery subsystem controller 164 detects that pressuresensor 178 measures a pressure above or below a predetermined range.Measured air/O.sub.2 pass-thru flow rate may be displayed on display102, 112(a), 112(b). Dosing and delivery info may be displayed ondisplay 102, 112(a), 112(b) along with confirmation of delivery.

In exemplary embodiments, gas analyzer subsystem 180 can detect afailure of NO sensor 182, a nitrogen dioxide gas sensor 186, and/or anoxygen gas sensor 188, where the gas analyzer subsystem controller 184may detect a failure of NO sensor 182 to ratio-metrically calculatedvalue of NO concentration for one or more flow control channels. If afailure or error is detected at the gas analyzer, then rather than losemonitoring the therapeutic gas delivery system can display theratio-metric delivered NO concentration from delivery or confirmatorysensors in place of the gas analyzer measured NO concentration and alertthe user of the issue.

In at least some instances, gas analyzer subsystem 180 may requirecalibration before being operatively associated with an inspiratory line213 and/or injector module 107 to sample therapeutic gas(es) and/orduring delivery of therapeutic gas to a patient to ensure the gasanalyzer subsystem 180 is functioning properly. For example, gasanalyzer subsystem 180 can perform calibrations (e.g., baselinecalibrations, span calibrations, etc.) of the gas sensor (e.g.,catalytic type electrochemical gas sensor, etc.) by sampling and/ormeasuring the concentration of target gases in a controlled sample(e.g., baseline sample, span sample, etc.), where a span sample is atarget gas (i.e., nitric oxide) with a specific known and controlledconcentration within a range of interest (e.g., 00 PPM, 25 PPM, 50 PPM,80 PPM, etc.) and/or where a baseline sample is a gas containing zeroconcentration of a target gas (i.e., conditioned ambient air containingzero nitric oxide). For example, a sample of ambient gas and/or span gascan be sampled via a sample line 119 that can be in fluid communicationwith valve 194. This gas sample can flow and/or be pulled to the gassensors (e.g., NO sensor 182, etc.) wherein the flow can regulated viavalve 194 (e.g., a three way valve, etc.) and/or sample pump 192. Sampleline flow can be measured using flow sensor 190. A gas sample fromambient gas and/or span gas, via sample line 119, can flow and/or bepulled to the gas sensors (e.g., NO sensor 182). Flow in sample line 119can be regulated via valve 194 (e.g., a three way valve, etc.) and/orsample pump 192. Sample line flow can be measured using flow sensor 190.

Therapeutic gas delivery system controller may be configured to executea program or algorithm which calculates run-time-to-empty using thevalues received by the therapeutic gas delivery system controller and/orstored in memory from a temperature sensor 130(a), 130(b), a gaspressure sensor 120(a), 120(b), therapeutic gas pressure regulator122(a), 122(b), flow sensor 146(a), 146,(b), 166, and gas sourceidentifier reader 131 (therapy gas concentration, either actual ortarget). To obtain the run-time-to-empty value, the volume oftherapeutic gas in the therapeutic gas source at a selected time-pointduring therapy may be calculated using the Boyle's Law or the Ideal GasLaw and the wetted volume of the therapeutic gas source. That is, usingthe temperature of the therapeutic gas, the therapeutic gas pressure,and the known wetted volume of the therapeutic gas source 116(a),116(b), the pressure of water vapor at the measured temperature issubtracted from total gas source pressure to obtain the pressure of thedry therapeutic gas. Boyle's Law (V.sub.a=p.sub.cV.sub.c/p.sub.a) or theIdeal Gas Law (PV=nRT) is applied to calculate the volume in liters ofthe dry therapy gas at the measured temperature. In various embodiments,the run-time-to-empty may be calculate continuously to display changesin gas source pressure, intermittently, or when a delivery dose is setor changed to reflect changes in the run-time-to-empty for the new setdose.

In various embodiments, oscillating run-time-to-empty values may not bedisplayed. To avoid oscillating run-time-to-empty values being displayedintermittent recalculation may be implemented to avoid rapid changes inpressure and/or temperature, and allow a specific run-time-to-emptyvalue to be displayed for a period of time sufficient for a user to readthe run-time-to-empty value.

An average therapeutic gas consumption rate may be derived using dataobtained from periodic and/or continuous measurements of a) averageL/min. measured by the flow controller or commanded to the flowcontrollers over a period of time, b) average ventilation flow ratemeasured by BCG flow sensors 108(a) and/or 108(b) over a period of time,or c) set dose in ppm and an average ventilation flow rate measured byBCG flow sensors 108(a) and/or 108(b) over a period of time, which givesan average therapy gas flow rate in L/min. to be delivered.

By way of example, calculation of average therapeutic gasdelivery/consumption rate using set dose and an average ventilation flowrate over a period of time is calculated as follows:

QNOset.sub.(n)={YNOset/(YNOcyl−YNOset)}Q.sub.i(n) (SLPM)

Where

QNOset=NO flow rate desired (SLPM)

Q.sub.a=Injector Module flow rate (SLPM)

YNOset is the delivery set-point, the user set NO

concentration value (ppm)

YNOcyl is NO cylinder concentration (ppm)

Run-time-to empty (RTE) for the selected time-point is then calculatedfrom the volume of therapy gas in the therapy gas source and theconsumption rate calculated by one of the above methods:

RTE=(Remaining cylinder volume-reserve volume-known purgesequences)/(average therapy gas consumptionrate(primary+secondary)+known leak rate).

In exemplary embodiments, algorithms can be executed (e.g., using theabove calculation) by system 100 which may be configured to leave someamount of gas pressure (i.e., gas volume) in the therapeutic gas source116(a), 116(b), etc. (the “reserve volume”) rather than running the gassource to empty. For example, the gas source can be a cylinder that maybe deemed “empty” to the user when the cylinder pressure reaches 300psi, 200 psi or 30 psi. This minimum pressure can be the minimumresidual pressure needed for the regulator to function, plus pressureloss through valves, conduits, etc upstream of the pressure regulator,and/or plus pressure required for purging. Further, this can be used tocompensate for delivery system 100 being configured to be for atherapeutic gas source that always has a pressure of at least, or morethan, 30 psi. In various embodiments, run-time-to-empty calculations mayalso take into account use of therapeutic gas for anticipated purges dueto for example a low set dose/flow rate.

In exemplary embodiments, the therapeutic gas delivery system controllermay be configured to automatically reduce the delivery dose to conservegas when run-time-to-empty calculations indicate the operatingtherapeutic gas source(s) 116(a), 116(b) is getting low and there is noback-up therapeutic gas source(s) 116(a), 116(b) available to supply thetherapeutic gas at a sufficient pressure. Further, to provide the lowerdose, the therapeutic gas delivery system 100 could ignore or bypass theminimum pressure threshold for the gas source, and continue deliveringthe therapeutic gas until the therapeutic gas source(s) 116(a), 116(b)is empty. In such instances, alarms may be provided. The above can bebeneficial as a lower dose may be safer than discontinuation of therapy,therefore a reduced dose may be provided to the patient. In variousembodiments, therapeutic gas delivery system controller may beconfigured to automatically reduce the delivery dose to conserve gaswhen high NO2 is detected to reduce the amount of NO available to reactwith O.sub.2. In various embodiments, the therapeutic gas may beprovided concurrently from two or more therapeutic gas source(s) 116(a),116(b) to provide a larger total volume of therapeutic gas at the lowerpressure(s) until empty.

In one or more embodiments, as described above, the therapeutic gasdelivery system controller may communicate the calculatedrun-time-to-empty for the current set dose to a central display 102and/or to a status display 112(a), 112(b) associated with a particulargas supply subsystem 110(a), 110(b) to notify the user of the run timeremaining for the particular therapeutic gas source 116(a), 116(b) in aparticular receptacle. When run-time-to-empty reaches predeterminedlevels, the therapeutic gas delivery system controller may alsocommunicate modified alarms to the central display 102 and/or to astatus display 112(a), 112(b) to indicate varying levels of criticality.For example a high level alarm may indicate that a half hour of run timeremains, a moderate level alarm may indicate that an hour of run timeremains, and a low level alarm may indicate that an hour and a half ofrun time remains. For another example, therapeutic gas delivery systemcontroller may activate an audible alarm on the therapy gas deliverysystem or transmit an alarm to a wireless device (e.g., smart phone) tonotify the user of remaining run-time. In one or more embodiments, atherapeutic gas delivery system comprising two or more therapeutic gassources may supply therapeutic gas from the therapeutic gas sourcehaving the shorter run-time-to-empty value. In various embodiments, thetherapeutic gas delivery system may seamlessly transition from a firsttherapeutic gas source to a second therapeutic gas source when the firsttherapeutic gas source has reached the intended run-time-to-empty value.In various embodiments, the calculated run-time-to-empty for the currentset dose and/or the various alarm levels may be communicated to ahospital information system. Alarms may sound when the therapeutic gasdelivery system 100 is operating on only one therapeutic gas source116(a), 116(b). Alarms may be triggered based on the run-time-to emptyvalue and/or therapeutic gas source 116(a), 116(b) pressure measured atgas pressure sensor 120(a), 120(b). Such alarms may be audible and/orvisual. In at least some instances the run-time-to-empty can be thecombined run-time-to-empty for both therapeutic gas sources, forexample, depicted as one value and/or in any other visual format (e.g.,graph, chart, image, etc.)

In various embodiments, display(s) 102, 112(a), 112(b), etc., mayprovide visual representation (e.g., graphical representation, bargraph, etc.) to a user visually indicating the remaining amount oftherapeutic gas available from the therapeutic gas source 116(a),116(b). This can be beneficial as the user can see when a therapeuticgas source 116(a), 116(b) will need to be replaced. A user mayanticipate change-over from an active therapeutic gas source to a second(e.g., unused, full) therapeutic gas source by observing the actual RTEvalue, or visual representation, shown on display(s) 102, 112(a),112(b). The visual representation may be displayed alongside the RTEvalue for each gas source, or instead of a RTE value when a dose is notset or flow through a flow control channel or an injector module 107 isnot detected. In addition, an alarm may be provided when a therapeuticgas source is getting low, or the therapeutic gas delivery system 100 isdown to only one operating therapeutic gas source. The therapeutic gasdelivery system 100 may provide an alarm and/or instructions for theuser to replace the depleted therapeutic gas source with a fulltherapeutic gas source. Displaying the actual RTE value(s) and/or visualindicators (e.g., bar graph, alarms, etc.) can allow the user to beaware of the remaining run time for the gas sources without having tolook for the reading on a pneumatic pressure gauge attached to the gassource regulator and/or such visual displays can make monitoring thetherapeutic gas delivery system 100 easier and help to avoid errors dueto misreading various gauges and mechanical settings. Having one or moredisplays showing a run-time-to-empty value on the front of the systemcan mitigate problems associated with users having very little, or no,warning before the pressure supplied by a therapeutic gas source isunable to satisfy input pressure requirements for therapeutic gaspressure regulator 122(a), 122(b) and/or flow control valve(s) 143(a),143(b), 163 and/or sensors. In various embodiments, the display(s) 102,112(a), 112(b) may provide redundancy by being configured to allow auser to operate the therapeutic gas delivery system 100 from any of thedisplays 102, 112(a), 112(b), for example where each display is a touchscreen that accepts user input.

In exemplary embodiments, implementation of two therapeutic gas sources116(a), 116(b) provides redundancy, where second therapeutic gas sources116(b) may supply therapeutic gas to a patient 203 when the firsttherapeutic gas sources 116(a) becomes depleted. For example, therapygas delivery to the patient is initiated from therapy gas source 116(a)and delivered to the patient as described above. Further, as therun-time-to empty reaches a minimum value predetermined by the userand/or the system 100, therapeutic gas delivery system controller mayclose shut off valve 126(a) and open shut off valve 126(b) to sourcetherapy gas delivery from second therapy gas source 116(b).

In one or more embodiments, therapeutic gas delivery system controllermay automatically adjust for varying gas source concentrations whenchanging over from a first therapeutic gas source 116(a) to a secondtherapeutic gas source 116(b) containing the same therapeutic gas at adifferent concentration. By way of example, to accomplish the above gassource concentration information can be provided by gas sourceidentifier 128(b), which can have recorded thereon the target and/oractual measured concentration of the therapeutic gas in therapeutic gassource 116(b). Further, as discussed above, gas source identifier 128(b)can also have recorded thereon additional data such as the identity ofthe therapy gas and/or its expiration date. In exemplary embodiments,use of the higher concentration therapeutic gas source may requiresystem 100 increase in the average injector module 107 flow rate beforedelivery of the therapeutic gas would begin, or a reduction intherapeutic gas flow rate through flow control valve(s) 143(a), 143(b),163, to maintain the same set dose to the patient 203. Similarly,injector module 107 flow rate may be reduced, and/or therapeutic gasflow rate through flow control valve(s) 143(a), 143(b), 163, may beincreased to maintain the same set dose to the patient 203 for a lowertherapeutic gas source 116(b) concentration.

If the therapeutic gases in therapeutic gas source 116(a) andtherapeutic gas source 116(b) have different concentrations, therapeuticgas delivery system controller may automatically instruct a purge of thetherapeutic gas delivery system, in which gas from the succeedingtherapeutic gas source 116(b) is flushed through the high pressure sideof the system, by opening purge valve 124(b) to evacuate all of thehigher or lower concentration therapeutic gas from the manifold beforeopening second shut off valve 126(b) to the rest of the system, inaddition to oxygen trapped that may form into NO2. In exemplaryembodiments, purging to the atmosphere can be through a dedicated purgeport in fluid communication with purge valve(s) 124(a), 124(b) toprevent exposure of the patient to purged gases (e.g., wrongconcentration, contaminated, NO.sub.2, etc.).

In exemplary embodiments, therapeutic gas delivery system controller mayadjust parameters accordingly in the therapeutic gas delivery algorithmcalculations to maintain the desired set dose taking into account thetherapeutic gas concentration in therapy gas source 116(b). In at leastsome instances, if the therapeutic gas in the succeeding therapy gassource 116(b) is different from the therapeutic gas in therapeutic gassource 116(a), therapeutic gas delivery system controller mayautomatically orchestrate, instruct orchestration of, a purge of thetherapeutic gas supply subsystem 110(a), 110(b) before opening shut offvalve 126(b) to evacuate all of the preceding therapy gas from theremainder of the system. Therapeutic gas delivery system controller maythen adjust parameters accordingly in the therapy gas delivery algorithmfor therapy gas source 116(b) to deliver the correct set dose to thepatient.

Pre-Use Verification Processes and/or Verification Processes

In exemplary embodiments, at least some aspect of the present inventionrelate to systems, methods, and/or process for, amongst other things,performing pre-use verifications by confirming the proper operation of atherapeutic gas delivery system 100, leaks, the proper functioning ofthe gas supply subsystem(s), gas delivery subsystem(s), and/or gasanalyzer subsystem(s), and by extension the proper functioning of thevalve(s), flow sensor(s), pressure sensor(s), detector(s), regulator(s),and/or subsystem controller(s), to name a few.

With respect to at least pre-use verifications of the present invention,some found previous pre-use procedures to be difficult and intimidating,and required extensive training. Exemplary embodiments of the presentinvention reduce and/or simplify the number and sequence of pre-useprocedures and/or increases patient safety by eliminating and/ormitigating risks associated with previous pre-use procedures. Forexample, abnormalities and/or failures of elements of system 100 mayresult in sudden discontinuation of therapeutic gas and thereby a suddenremoval of therapy to a patient, which can result in potential lifethreatening hazard (e.g., rebound hypertension); however, using systems,methods, and processes for, amongst other things, performing pre-useverifications can result in detection of an abnormality and/or failureduring the pre-use performance verification test and mitigation of apotentially life threatening hazard. For example, detection of anabnormality and/or failure during the pre-use performance verificationcan effectively convert a potential hazard from the sudden removal oftherapy to a delay of therapy (e.g., time to get another device), whichcan be much less severe.

Purging of system 100 may be important as air/O.sub.2/contaminants mayenter into components of system 100 configured to fluidly communicateNO. This can be problematic as NO may react with thisair/O.sub.2/contaminants, for example, generating NO2. Theseair/O.sub.2/contaminants may enter system 100 via physical connection oftherapeutic gas source 116(a), 116(b) to gas supply subsystem 110(a),110(b), for example, trapping air/O.sub.2/contaminants between thetherapeutic gas source valve 117(a), 117(b) and the connection valve118(a), 118(b).

In at least some instances, after properly receiving and/or verifyingtherapeutic gas source 116(a), 116(b), the therapeutic gas deliverysystem controller may initiate a purge sequence of the conduit/manifoldbetween the therapeutic gas source valve 117(a), 117(b) and the closedshut off valve 126(a), 126(b), wherein the purged gas may exit theconduit/manifold via opened purge valve 124(a), 124(b). In variousembodiments, a purge sequence may be initiated within a fraction of asecond and/or within 2 seconds of detecting a properly receivedtherapeutic gas source 116(a), 116(b). This purge may avoid thetherapeutic gas from coming into prolonged contact with trappedair/O.sub.2/contaminants introduced, for example, by the fluidconnection between gas source valve 117(a), 117(b) and connection valve118(a), 118(b).

In one or more embodiments, a conduit/manifold between connection valve118(a), 118(b) and closed shut off valve 126(a), 126(b) may be purged byopening purge valve 124(a), 124(b) when therapeutic gas source 116(a),116(b) is removed, for example, as indicated by gas source detector132(a), 132(b). This purge may be used to reduce pressure betweenconnection valve 118(a), 118(b) and closed shut off valve 126(a),126(b), and/or evacuate stale gas from the manifold. As used herein,“stale” means that the therapeutic gas source may have reacted withair/O.sub.2, unacceptable levels of NO.sub.2 may have built up in themanifold, and/or other contaminants (e.g., H.sub.2O, rust, etc.) mayhave entered the manifold or accumulated over time. The purge may lowerthe high pressure in the manifold back to just below a minimum cutoff of200 PSI pressure (residual pressure), such that insertion of a newtherapeutic gas source will trigger a higher pressure reading at gaspressure sensor 120(a), 120(b). Therapeutic gas delivery system 100 maynot rely on gas pressure sensor 120(a), 120(b) to detect the presence oftherapeutic gas source 116(a), 116(b) in fluid communication with theconduit/manifold 119(a), 119(b) because the response time of pressuresensor 120(a), 120(b) may be too slow to initiate a purge quickly enoughto avoid gas reactions, and/or connection valve 118(a), 118(b) may haveretained a gas pressure within conduit/manifold 119(a), 119(b)commensurate with the pressure in the mated therapeutic gas source116(a), 116(b) that prevents a pressure change from being measured.

In one or more embodiments, purging sequences may be initiated, forexample, by the therapeutic gas system controller, when therapeutic gassource 116(a), 116(b) is received (e.g., coupling member 114(a), 114(b)of therapeutic gas source 116(a), 116(b) mated with gas source coupling115(a), 115(b); load handle (not shown) operatively manipulated; etc.)and/or during delivery of therapeutic gas to a patient.

Further to air/O.sub.2/contaminants that may enter when therapeutic gassource 116(a), 116(b) is received (e.g., via physical connection oftherapeutic gas source 116(a), 116(b) to gas supply subsystem 110(a),110(b), etc.), low rates of NO consumption may trigger the need forpurging sequences from the therapeutic gas source 116(a), 116(b) and allgas conduits/components in use. This build-up of NO.sub.2 may also occurif oxygen permeation rate through the soft elastomer materials ofconduits and/or seals is sufficient for NO gas volume moving through thesystem at a low rate to react causing the NO.sub.2 conversion rate toincrease. Conduit lengths, seals, and dead spaces may be reduced oreliminated to keep molecule of NO leaving the gas source and headingtowards the patient circuit moving at the fastest rate practicallypossible to reduce dwell time. In at least some instances purgingsequences may be more frequent when therapeutic gas consumption ratesare low.

In at least some instances, purging sequences may be initiated duringdelivery of therapeutic gas to a patient because, for example, thedelivery dose may be sufficiently low that the flow rate of therapeuticgas through one or more of the flow control channels is sufficiently lowto allow a build-up of NO.sub.2 on the high pressure side of shut offvalve 126(a), 126(b), and/or the upstream side of primary flow controlvalve 143(a), 143(b), and/or secondary flow control valve 163. Asdescribed above, these purging sequences of the gas flow path to a vent(e.g., opened purge valve) removes the built-up NO.sub.2 and othercontaminants.

Similarly, purging sequences may be initiated when therapeutic gasdelivery system 100, first gas supply subsystem 110(a) and/or second gassupply subsystem 110(b), have not been in use for a prolonged and/orpredetermined amount of time (e.g., 10 min, 30 min, 1 hr, 6 hours, 12hours, 24 hours, etc.). Purging sequences may utilize gas from a gassource (e.g., therapeutic gas source, etc.) and/or the purge may utilizepressurized gas contained between connection valve 118(a), 118(b) and aclosed shut off valve 126(a), 126(b). Purging sequences described hereinmay be triggered upon detection of no therapeutic gas source, forexample, as indicated by gas source detector 132(a), 132(b), load handleand/or gas source identification sensor 128(a), 128(b).

In various embodiments, purging sequences described herein may enablesystem 100 to maintain receptacle/gas supply subsystem 110(a), 110(b)primed for receiving therapeutic gas source 116(a), 116(b) and/or primedfor seamlessly transition from one therapeutic gas source to anothertherapeutic gas source. As described above, seamless transition may beanticipated based on pressure and/or RTE calculation for the active(i.e., in use) therapeutic gas source 116(a), 116(b). Further, inexemplary embodiments, the duration and/or volume of gas used forpurging sequences can be reduced (e.g., mitigate therapeutic gas waste,mitigate the amount of therapeutic gas purged/wasted into thesurrounding environment, etc.). By way of example, orifices of the purgevalves can be calibrated such that purge flow rates may be known, andtherefore the volume of gas used for purging sequences can be dependenton purge valve open time.

In one or more embodiments, purging sequences may comprise a series ofintermittent openings of purge valve 124(a), 124(b), and/or all of theflow control channel valves for a period of about 1 second to about 10seconds followed by a period of about 1 second to about 10 secondsduring which purge valve 124(a), 124(b), and/or all of the flow controlchannel valves, are closed. This intermittent opening and closing may berepeated 5, 10, 15, 20 times. In various embodiments, purging sequencesmay be increased to prime the therapeutic gas source for use morequickly, for example, by using the therapeutic gas in a continuous purgethat may last from about 1 minute to about 10 minutes, or any time inbetween.

In one or more embodiments, therapeutic gas delivery system 100 may notpower down until therapeutic gas sources 116(a), 116(b) are removed(e.g., released from receptacle/gas supply subsystem 110(a), 110(b),etc.). To at least prevent build-up of NO.sub.2 and/or reduce waste oftherapeutic gas, therapeutic gas delivery system 100 can require removalof therapeutic gas sources 116(a), 116(b) before shutting therapeuticgas delivery system 100 off. In at least some instances, an alarm may beprovided until all therapeutic gas sources 116(a), 116(b) are removed.After removal of the therapeutic gas sources 116(a), 116(b), purging ofthe now empty bay(s) may be conducted, as described above. In variousembodiments, a purge may not be initiated if the run-time-to-empty valueindicates the therapeutic gas source is low (e.g., in a medium or highalarm state) in order to conserve therapeutic gas for delivery to thepatient. In exemplary embodiments, when powered on, if therapeutic gasdelivery system 100 detects a cylinder has been received the system caninitiate a purge and/or alert.

In exemplary embodiments, purging sequences can be initiated to purgefluid pathways downstream of shut off valve 126(a), 126(b) such asconduits (e.g., conduit 101(a), 101(b), 172, etc.), flow controlchannels (e.g., flow control channels 141(a), 141(b), 161, etc.), and/orany other fluid pathways and/or components downstream of shut off valve126(a), 126(b). By way of example, to purge downstream, shut off valve126(a), 126(b) may be opened while purge valve 124(a), 124(b) is closed,enabling flow of therapeutic gas from the gas supply subsystem to atleast one of the one or more flow control channels 141(a), 141(b), 161and in turn to an egress from therapeutic gas delivery system 100 (e.g.,purge valve, outlet from therapeutic gas delivery system 100, etc.). Invarious embodiments, primary delivery subsystem 140 and/or secondarydelivery subsystem may include at least one purge valve in fluidcommunication with flow control channel 141(a), flow control channel141(b), flow control channel 161(a), and/or at least one purge valve influid communication with injector module 107. In various embodiments,the corresponding shut off valves for each of the flow control channelsmay be selectively and/or sequentially opened and closed to purge theflow control channels. By way of example, when one flow control channelhas been purged, the associated shut off valve 142(a), 142(b), 162, maybe closed and the shut off valve for the next flow control channel maybe opened.

In one or more embodiments, system 100 may perform pre-use verificationprocedures and/or during delivery of therapeutic gas to a patient forleaks by pressurizing, and/or prompting a user to install a therapeuticgas source, the gas supply subsystem at least between connection valve118(a), 118(b) and closed shut off valve 126(a), 126(b) to a pressureabove atmospheric pressure, monitoring the pressure between connectionvalve 118(a), 118(b) and closed shut off valve 126(a), 126(b) with gaspressure sensor 120(a), 120(b) for a predetermined time period, andpresenting an alarm if the pressure between connection valve 118(a),118(b) and closed shut off valve 126(a), 126(b) decreases greater thanan expected amount over a predetermined time period (e.g., decrease inpressure due to a leak, etc.). In various embodiments, the predeterminedtime period may be a fixed time period, for example 30 seconds, 5 min,10 min, 15 min, 20 min, 30 seconds or the time period may be between theinitiation of a pre-use verification procedure and completion of thepre-use verification procedure, embodiments of which are describedherein. In various embodiments, a greater than expected amount may beany drop in pressure over a short period (e.g., 5 min, 10 min, 15 min)or a drop in pressure larger than previously seen for a known leak-tightsystem and/or tested system for longer periods of time (e.g., 30seconds, 20 min, 30 min, time for check-out, etc.).

In at least some embodiments, system 100 may perform checks for leakswithin system 100, for example, during pre-use verification and/or whendelivering therapeutic gas (e.g., when delivering therapeutic gas to apatient, etc.). Similar to checking for leaks between connection valve118(a), 118(b) and closed shut off valve 126(a), 126(b), system leakscan be identified by pressurizing, and/or prompting a user to install atherapeutic gas source, the system to a known pressure (e.g., pressureabove atmospheric pressure, etc.), opening and/or closing valves withinsystem 100 and monitoring the pressure between the various open and/orclosed valves with pressure sensors. Further, in at least someinstances, system 100 may perform checks for leaks within system 100when delivering therapeutic gas (e.g., background leak checks) bymonitoring pressure sensors affiliated with system 100 for decreases inpressure that are greater than an expected amount over a predeterminedtime period.

In at least some embodiments, checks for leaks performed by system 100may factor in the therapeutic gas used for pre-use verification fromboth gas sources, purging, etc.

In one or more embodiments, gas flow rate measured at each of deliveryflow sensors 146(a), 146(b), 166 may be compared against the gas flowrate through confirmatory flow sensors 148(a), 148(b), 168 in serieswith delivery flow sensors 146(a), 146(b), 166 for the associated flowcontrol channel. In various embodiments, an alarm, recommend replacingat least one of the sensors, perform verification processes (describedbelow in greater detail) to confirm which sensor is not functioningproperly, and/or provide flow information from the functioning flowsensor, etc. may be provided if there is a discrepancy between the gasflow rate through the delivery flow sensor and the gas flow rate throughthe confirmatory flow sensor, where a discrepancy greater than athreshold amount of about 10%, or about 7%, or about 5%, or about 2.5%,or about 2%, or about 1%, or about 0.5% triggers an alarm.

Aspect of the present invention relates to a method of confirming theproper functioning of gas delivery and injector module operation. Incertain embodiments, therapeutic gas delivery system controller mayfurther comprise an automated performance verifications during deliveryof therapeutic gas and/or pre-use performance verification algorithmthat purge at least a portion of therapeutic gas delivery system 100upon installation of therapeutic gas source 116(a), 116(b) and/or duringdelivery of therapeutic gas, and verifies operability of selectedcomponents of therapeutic gas delivery system 100 before use (e.g.,pre-use) and/or during use (e.g., during delivery of therapeutic gas).

In one or more embodiments, pre-use performance verification and/orperformance verification during delivery of therapeutic gas can comprisethe therapeutic gas delivery system controller comparing theconcentration of the therapeutic gas reported by the gas analyzer 180 tothe ratio-metric calculation(s) based on the flow rate values reportedby flow sensors 146(a), 146(b), 166, 148(a), 148(b), 168 for each offlow control channels 141(a), 141(b), 161. A result of the comparisonshowing a different gas analyzer value for one flow control channel mayindicate that the flow control valve, sensor, and/or componentassociated with that flow control channel is not functioning properly,whereas a different gas analyzer value compared to the ratio-metricvalue for all flow control channels may indicate that the therapeuticgas sensor is out of calibration. The use of redundant flow sensors146(a), 146(b), 166, 148(a), 148(b), 168 in each of the flow controlchannels allows the system and/or user to pinpoint which component maynot be functioning through cross checking. In this manner, it can bedetermined if a flow valve 143(a), 143(b), 163 needs calibration or thegas analyzer 180 needs high calibration. In various embodiments, gasanalyzer values and/or ratio-metric values within pre-set tolerance(e.g. +−20% of set dose) can be considered an acceptable variation. Theredundant ratio-metric calculations for flow control channels 141(a),141(b), 161 can provide a basis to correct the output of the gasanalyzer without the need for calibration gas if the ratio-metriccalculations are all in agreement with one another. The differencebetween the calculated ratio-metric values and the measured gas analyzervalue indicates the amount by which the gas analyzer is out ofcalibration. The output of the gas analyzer can then be compensated for.The gas analyzer 180 can references room air to prevent over-saturationduring measurements. If a failure or error is detected at the gasanalyzer, then rather than lose monitoring the device can display theratio-metric delivered NO concentration from delivery or spy sensors inplace of the gas analyzer measured NO concentration and alert the userof the issue.

In various embodiments, a user may be instructed to connect the injectormodule 107 with a particular orientation to the low pressure outlet port167 to test the injector module and secondary delivery subsystem 160, asshown for example in FIG. 5 . In various embodiments, an alarm,recommendation of replacing at least one of the sensors, performverification processes (described below in greater detail) to confirmwhich sensor is not functioning properly, and/or flow information fromthe functioning flow sensor, etc. may be provided if the breathing gasflow rates measured at low pressure confirmatory flow sensor 176, lowpressure delivery flow sensor 174, injector module confirmatory flowsensor 108(b), or injector module delivery flow sensor 108(a) differsfrom the other measured breathing gas flow rates by greater than athreshold amount, where the threshold amount may be a difference ofabout 10%, or about 7%, or about 5%, or about 2.5%, or about 2%, orabout 1% A, or about 0.5% between two measured flow rates, or betweenany one of the sensor measured values and the average flow rate. Thethreshold amount may depend on the accuracy and tolerances of the flowsensors used in the system.

In various embodiments, pre-use performance verification and/orperformance verifications during delivery of therapeutic gas may furthercomprise adjusting flow control valve 163 to provide a stream oftherapeutic gas at an intended therapeutic gas flow rate; anddetermining if flow control valve 163 is properly functioning, where thesubsystem flow control valve is in fluid communication with the lowpressure outlet port. In various embodiments, a subsystem flow controlvalve may be adjusted to be completely open to provide the stream oftherapeutic gas at a maximum therapeutic gas flow rate.

In one or more embodiments, the combined therapeutic gas flow rate andbreathing gas flow rate may be measured at injector module delivery flowsensor 108(a) and injector module confirmatory flow sensor 108(b) influid communication with low pressure outlet port 167; and three-wayvalve 170 may be switched to divert the stream of therapeutic gas to analternative flow path, where the three-way valve is upstream from and influid communication with the low pressure outlet port, and the subsystemflow control valve is upstream from and in fluid communication with thethree-way valve, to determine if three-way valve 170 functioned properlyby determining if the combined therapeutic gas flow rate and breathinggas flow rate decreased by the therapeutic gas flow rate when thethree-way valve was switched to the alternative flow path. In variousembodiments, the breathing gas flow rate may be measured at injectormodule delivery flow sensor 108(a) and injector module confirmatory flowsensor 108(b). In an exemplary embodiment, flow control valve 163 may beset to the highest flow rate, and a step change (e.g., increase) can beobserve on injector module delivery flow sensor 108(a) and injectormodule confirmatory flow sensor 108(b). When three-way valve 170 isswitched to divert the gas flow from injector module 107, a decrease ingas flow rate can be detected downstream by injector module deliveryflow sensor 108(a) and injector module confirmatory flow sensor 108(b).Similarly, when subsystem flow control valve 163 is set to a minimum orzero flow rate, a decrease in gas flow rate can be detected downstreamby injector module delivery flow sensor 108(a) and injector moduleconfirmatory flow sensor 108(b). This can be repeated several times.

In various embodiments, a flow rate may be measured at two or moresecondary delivery subsystem flow sensors, wherein flow sensors 166, 168are upstream from and in fluid communication with three-way valve 170;and the flow rates measured at each of the two or more subsystem flowsensors may be compared to determine if the two or more subsystem flowsensors are in agreement. In various embodiments, therapeutic gasblending ratio may be calculated from the measured flow rate measured byat least one of the two or more subsystem flow sensors and from thebreathing gas flow rate measured by the low pressure delivery flowsensor; and comparing the calculated therapeutic gas blending ratio tothe measured concentration of therapeutic gas exiting the injectormodule.

In various embodiments, each of the one or more shut off valves and/orflow control valves for each of the one of the one or more flow controlchannels may be selectively and/or sequentially opened and closed toconfirm functionality and/or deliver a controlled flow of therapeuticgas to the injector module. In various embodiments, the gas analyzerconfirms flow control channel(s) 141(a), 141(b) are functioning properlyand providing the intended dose. Measurement of flow rates by redundantflow sensors can detect discrepancies between the flow controllers, flowsensors, and/or flow control channels. A purge of each flow controlchannel and delivery line 111 can also occur while the confirmation offlow control is being conducted. In various embodiments, the gasanalyzer subsystem may reference room air while the purge is occurring.

In an alternative scenario the gas analyzer may be able to select tosample from within a pre-use verification port, so that the sample linedoes not need to be connected during performance verification.

In one or more embodiments, therapeutic gas may be delivered to theinjection port of the injector module 107 through delivery line 111, agas sample may be collected by sample-T 121 and directed to the gasanalyzer to confirm the gas flow rate of therapeutic gas through flowcontrol channel(s) 141(a), 141(b) provides an intended dose.

In various embodiments, system 100 can automatically compensate fordifferent therapeutic gas source concentrations, for example, inresponse to pre-use verification. By way of example, system 100 canadjust flow valve 163 output during the performance verification toreduce the flow rate to half if the therapeutic gas source concentrationis doubled.

In various embodiments, the system may instruct a user to disconnect theinjector module from the low pressure outlet port and connect theinjector module to ventilator breathing circuit 213. In variousembodiments, the direction of gas flow from a ventilator through theinjector module may be confirmed by bi-directional flow sensors 108(a),108(b) of injector module 107.

In various embodiments, the system may instruct a user to disconnect themain electrical feed to therapeutic gas delivery system 100 to checkthat the backup battery is charged and functioning.

In various embodiments, the system may go through a post-use/shut-downverification procedure which may comprise relaying patient informationdata to the medical facility's information system.

In various embodiments, the system may prompt a user to removetherapeutic gas source(s) 116(a), 116(b), and verify that therapeuticgas source(s) 116(a), 116(b) have been removed through gas sourcedetector 132(a), 132(b). At such time, the system may go through ashut-down purge as discussed above.

In various embodiments, the system may prompt a user to clean injectormodule 107 and/or provide instructions for cleaning injector module 107.In various embodiments, the system may prompt a user if the system isdue for service.

One or more embodiments of the present invention provide an exemplarypre-use performance verification procedures, in which the followingsteps and/or procedures may be performed to ensure the properfunctioning of a therapeutic gas delivery system 100; determine if thereare leaks; ensure the proper functioning of the gas supply subsystem(s),gas delivery subsystem(s), and/or gas analyzer subsystem(s), and byextension the proper functioning of the valve(s), flow sensor(s),pressure sensor(s), detector(s), regulator(s), and/or subsystemcontroller(s). However, it is to be understood that any of these stepsmay be omitted or performed in a different order, or additional stepsmay be performed in addition those specifically indicated below.Furthermore, some of these steps may be performed concurrently,particularly if the steps are performed by components in separatesubsystems and/or at least some of these steps may be performed duringdelivery of therapeutic gas to a patient.

Referring to FIGS. 4A-4C, an exemplary pre-use performance verificationprocedure is depicted. At step 402, therapeutic gas delivery system 100is started up (e.g., powered on by user, etc.). When started up, anyand/or all subsystems (e.g., first gas supply subsystem 110(a), secondgas supply subsystem 110(b), primary gas delivery subsystem 140,secondary gas delivery subsystem 160, and/or gas analyzing subsystem180, etc.) can be booted up. At step 404, therapeutic gas deliverysystem 100 can confirm whether proper boot up of each subsystemoccurred. If all subsystems properly boot then an initial purge sequencecan begin, at step 408, and the purge can be verified as beingsuccessful, at step 410.

If any and/or all performance verifications process fail therapeutic gasdelivery system 100 can undergo failure processes, at step 406, whereintherapeutic gas delivery system 100 can alarm the user (e.g., alarmprovided on input interface 102, 106, alarm provided on displays 112(a),112(b), etc.), log the failure (e.g., store information in memoryaffiliated with system 100, for example, in an error log), indicate thesource of failure and/or recommend a course of action (e.g., changesetup, change component, etc.), shut down system if failure is critical,continue the performance verification process, and/or allow delivery oftherapeutic gas to the patient, to name a few.

In exemplary embodiments, an initial purge sequence can be initiated bysystem 100, wherein residual pressure gas and/or gas in system 100 canbe purged (e.g., via purge valves, via outlets, etc.). Residual pressureand/or gas can be from therapeutic gas sources that were previouslyreceived by system 100. For example, previously received therapeutic gassources may be from a previous use of system 100 and/or from a userinserting a therapeutic gas source prior to turning on therapeutic gassystem 100. If the initial purge sequence was not successful, thentherapeutic gas delivery system 100 can proceed to failure processes, atstep 406. If the initial purge sequence is successful, therapeutic gasdelivery system 100 may then receive the therapeutic gas source, at step412, for example, as described above.

For ease, the exemplary pre-use performance verification procedures aredepicted as being for two cylinders. This is merely for ease and is inno way meant to be a limitation. Similar techniques are envisioned fortherapeutic gas delivery systems capable of receiving therapeutic gasfrom any number of sources.

At step 414(a), 414(b), received therapeutic gas sources can be detectedby therapeutic gas delivery system 100 (e.g., using the techniquesdescribed above). In one or more embodiments, therapeutic gas source116(a), 116(b) can be received by receptacle/gas supply subsystem110(a), 110(b). To be received by receptacle/gas supply subsystem110(a), 110(b), coupling member 114(a), 114(b) of therapeutic gas source116(a), 116(b) may be required to mate with gas source coupling 115(a),115(b) of receptacle/gas supply subsystem 110(a), 110(b). After beingreceived, therapeutic gas source 116(a), 116(b) can be actuated (opened)thereby placing therapeutic gas source 116(a), 116(b) in fluidcommunication with gas pressure sensor 120(a), 120(b), which measuresthe pressure of the gas in therapeutic gas source 116(a), 116(b).

In one or more embodiments, therapeutic gas source 116(a), 116(b) may beautomatically detected when a load handle (not shown) is operativelymanipulated to release and/or lock therapeutic gas source 116(a), 116(b)with gas supply subsystem 110(a), 110(b) and/or gas source detector132(a), 132(b) detects a therapeutic gas source. In various embodiments,gas source detector 132(a), 132(b) may be operatively associated withthe load handle, where gas source detector 132(a), 132(b) detects when aload handle has been operatively manipulated. In various embodiments,gas source detector 132(a), 132(b) may be operatively associated withthe gas source coupling 115(a), 115(b), where the gas source detector132(a), 132(b) detects when matching coupling member 114(a), 114(b) oftherapeutic gas source 116(a), 116(b) has been mated with the gas sourcecoupling 115(a), 115(b).

At step 416(a), 416(b), data can be read in to confirm the correctcylinder has been received, for example, using the techniques describedabove. In exemplary embodiments, when received by therapeutic gasdelivery system 100, gas source identifier reader 131(a), 131(b) canread gas source identifier 128(a), 128(b), which has recorded thereonthe actual measured concentration of the therapeutic gas in gas source116(a), 116(b) and/or the manufacturer's target gas concentration fortherapeutic gas source 116(a), 116(b). Gas source identifier 128(a),128(b) may also have recorded thereon additional data such as, but notlimited to, the wetted volume of the gas source, the identity of thetherapeutic gas, and/or its expiration date, to name a few. Datarecorded on gas source identifier 128(a), 128(b) and gas pressuremeasured by gas pressure sensor 120(a), 120(b) can be communicated totherapeutic gas delivery system controller and stored in memory.

In various embodiments, the therapeutic gas delivery system controllermay maintain shut off valve 126(a), 126(b) in a closed state untilcompletion of verification analysis of the therapeutic gas source data,and keep therapeutic gas source closed off from the gas deliverysubsystems downstream from shut off valve 126(a), 126(b) if incorrectinformation is detected (e.g. expired gas source, concentration out ofrange, wetted volume out of range, wrong therapeutic gas, etc.)

In one or more embodiments, the therapeutic gas delivery systemcontroller may prompt a user to install a therapeutic gas source if anincorrect therapeutic gas source is received. By way of example, thepresence of a correct or incorrect therapeutic gas source 116(a), 116(b)received by gas supply subsystem 110(a), 110(b) may be determined byanalyzing therapeutic gas source data on and/or affiliated with gassource identifier 128(a), 128(b), which may be received by gas sourceidentifier reader 131(a), 131(b). In exemplary embodiments, at any timeduring use (e.g., during pre-use verification procedures, duringdelivery of therapeutic gas to a patient, etc.), data (e.g., therapeuticgas source data) on and/or affiliated with gas source identifier 128(a),128(b) can be analyzed, for example, by the therapeutic gas deliverysystem controller, to determine if the wrong therapeutic gas is coupledto the system, the therapeutic gas is expired, the therapeutic gas isthe wrong concentration, the therapeutic gas source contains the correcttherapeutic gas, the therapeutic gas is at sufficient pressure, etc.

In at least some embodiments, the therapeutic gas delivery systemcontroller may prompt a user to install a therapeutic gas source if thereceived therapeutic gas source is determined to be empty and/or doesnot meet the minimum threshold (e.g., minimum threshold pressure). Byway of example, the therapeutic gas delivery system controller maydetect that gas supply subsystem 110(a), 110(b) is empty and/or does notmeet the minimum threshold pressure using information communicated fromgas pressure sensor 120(a), 120(b) indicative of the pressure of areceived therapeutic gas source 116(a), 116(b).

In one or more embodiments, therapeutic gas delivery system 100 detectswhen a therapeutic gas source is installed and reads the affiliatedinformation from the therapeutic gas source identifier attached to thegas source. In various embodiments, the therapeutic gas delivery systemwill confirm that the information from the therapeutic gas sourceidentifier matches the expected identifier characteristics of thetherapeutic gas. In exemplary embodiments, if the affiliated informationfrom the therapeutic gas source identifier is found acceptable, thetherapeutic gas delivery system may initiate a performance verificationprocess during delivery of therapeutic gas.

At step 418(a), 418(b), after properly receiving and/or verifyingtherapeutic gas source 116(a), 116(b), the therapeutic gas deliverysystem controller may purge the system; verify the purge was successfulby, for example, analyzing the concentration of the therapeutic gasand/or measuring the current detected through valves; and/or check allother related therapeutic gas delivery system components. If notsuccessful and/or checks of other related components fail thentherapeutic gas delivery system 100 can proceed to failure processes, atstep 406.

At step 422, any and/or all flow sensors (e.g., flow sensors andcorresponding confirmatory flow sensors, etc.) can be verified as noflow measurements should be seen because no gas flow has been initiated.If flow is measured (e.g., when no flow should be measured), therapeuticgas delivery system 100 can proceed to failure processes, at step 406,for example, as this can be indicative of a leak and/or sensor failure.

At step 426, therapeutic gas delivery system 100 can prompt users toattach a low pressure gas supply to the low pressure inlet port and, inat least some instances, set the low pressure gas supply flow to a knownflow rate (e.g., 10 SLPM, etc.).

At step 428, flow can be detected and if flow is measured in the wrongdirection (e.g., user attached low pressure supply to the low pressureoutlet port, etc.)

the user can be prompted re-attach the low pressure gas supply (e.g.,returning to step 426). In exemplary embodiment, a flow of air/O.sub.2should be detected by the low pressure delivery flow sensor 174 and thelow pressure confirmatory flow sensor 176. In various embodiments, theair/O.sub.2 flow source to check the flow sensors 174, 176, 108(a),108(b) may be air/O.sub.2 from a regulated wall supply, a compressed gascylinder supply, or a pump, which may be internal or external to the gasdelivery system 100. A pump, regulated wall supply, or compressed gascylinder supply may be connected and/or activated by user. A pump mayprovide waveforms to test the dynamic measurement range of the flowsensors. Bi-directional pass-thru sensors may verify correct setup ofair/O.sub.2 inlet connection for the performance verification.

In various embodiments, low pressure outlet port 167 is used for bothconnection to an assisted breathing apparatus for delivery oftherapeutic gas and/or for connection of an injector module 107 for thepre-use verification procedure. Use of the same low pressure outlet port167 for both functions provides a means to simplify (e.g, reducingand/or eliminating operator error, etc.) the pre-use verificationprocedures with fewer user steps for check-out of primary delivery,backup delivery and monitoring systems. Low pressure outlet port 167 mayalso serve as storage location for injector module 107 by providing aknown and obvious location for the injector module to be located whennot in use. In various embodiments, low pressure inlet port 165 and lowpressure outlet port 167 may comprise connectors, for example quickdisconnect gas connectors, hose barb connectors, and hose couplings, orthe low pressure outlet port 167 comprise an adaptor configured anddimensioned to connect directly to the injector module. In variousembodiments, a disposable and/or sterilizable adapter that connects tothe injector module may be used to connect to low pressure outlet port167 for the performance verification. This allows for separation of thedevice, which is not sterilized, and injector module 107 which may besterilized.

At step 430, therapeutic gas delivery system 100 can prompt users toattach the injector module 107 such that, at step 432, no flow should beseen by injector module delivery flow sensor 108(a) and/or injectormodule confirmatory flow sensor 108(b). For example, the user may beprompted to place the injector module in electrical communication withtherapeutic gas delivery system 100 while the injector module is notexposed to gas flow. If flow is detected by injector module deliveryflow sensor 108(a) and/or injector module confirmatory flow sensor108(b) the user may be instructed to replace the injector module as oneof the flow sensors may be working improperly, for example, at step 406.

At step 434, therapeutic gas delivery system 100 can prompt users toattach the injector module 107 to low pressure outlet port 167, asdepicted in FIG. 5 , such that low pressure flow can be detected by atleast injector module delivery flow sensor 108(a) and/or injector moduleconfirmatory flow sensor 108(b), at step 436. For example, a user may beinstructed to attach the injector module 107 to the low pressure outletport for testing. If flow is not detected by injector module deliveryflow sensor 108(a) and/or injector module confirmatory flow sensor108(b) the user may be instructed to replace the injector module as oneof the flow sensors may be working improperly, for example, at step 406.In various embodiments, the direction of gas flow through the injectormodule may be determined by bi-direction flow sensors 108(a), 108(b).

In one or more embodiments, performance verification can compriseattaching an injector module at low pressure outlet port 167; attachinga low pressure gas supply to low pressure inlet port 165, where the lowpressure gas supply (e.g., regulated hospital wall outlet/externalsupply/cylinder) provides a flow of breathing gas at a breathing gasflow rate, and where the low pressure inlet port is in fluidcommunication with the low pressure outlet port; measuring the breathinggas flow rate from the low pressure gas supply at low pressure deliveryflow sensor 174 and/or at low pressure confirmatory flow sensor 176,where low pressure delivery flow sensor 174 and low pressureconfirmatory flow sensor 176 are in fluid communication with the lowpressure inlet port and the low pressure outlet port; measuring thebreathing gas flow rate from the low pressure gas supply at injectormodule delivery flow sensor 108(a) and/or injector module confirmatoryflow sensor 108(b), wherein the injector module delivery flow sensor andthe injector module confirmatory flow sensor are in fluid communicationwith low pressure outlet port 167; and determining if one of thebreathing gas flow rates measured at low pressure confirmatory flowsensor 176, low pressure delivery flow sensor 174, injector moduleconfirmatory flow sensor 108(b), or injector module delivery flow sensor108(a) differs from the other measured breathing gas flow rates bygreater than a threshold amount. Air/O2 flow rate may be in the range ofabout 0-60 SLPM, and may be detected as flowing in a forward direction.Placing the delivery flow sensors (e.g. injector module sensors and flowsensors) and confirmatory flow sensors in series facilitates detectionof a single flow sensor in the fluid flow path that is not workingand/or providing readings that do not match the others.

In exemplary embodiments, therapeutic gas delivery system 100 candetermine when injector module 107 has been coupled to low pressureoutlet port backwards. This can be accomplished because, amongst otherthings, the injector module delivery flow sensor and/or the injectormodule confirmatory flow sensor can be bi-directional flow sensorsconfigured to determine the direction of gas flow through the injectormodule 107. In various embodiments, the injector module delivery flowsensor and the injector module confirmatory flow sensor are arranged inlocated relative to each other in series, parallel, skewed, and/or anyother configuration.

At step 438, in exemplary embodiments, therapeutic gas delivery system100 can deliver air/O2 through secondary delivery sub system 160 (e.g.,received from a therapeutic gas source) to injector module 107 to atleast verify injector module delivery flow sensor 108(a), injectormodule confirmatory flow sensor 108(b), flow sensor 174, and/orconfirmatory flow sensor 176. In this configuration, the same flow ofgas should be detected by each of injector module delivery flow sensor108(a), injector module confirmatory flow sensor 108(b), flow sensor174, and/or confirmatory flow sensor 176. If any flow sensors are foundto not be functioning properly (e.g., measuring a different flow ratethan two other flow sensors) then therapeutic gas delivery system 100can undergo failure processes, at step 406.

By way of example, in exemplary embodiments, after performanceverification has confirmed that injector module confirmatory flow sensor108(b) and injector module delivery flow sensor 108(a) are bothfunctioning properly, and low pressure delivery flow sensor 174 and lowpressure confirmatory flow sensor 176 are both functioning properly,secondary delivery flow sensor 166 and secondary confirmatory flowsensor 168 may be tested. In various embodiments, the gas flow rate maybe measured by secondary delivery flow sensor 166 and secondaryconfirmatory flow sensor 168 and compared to the incremental gas flowrate measured by injector module delivery flow sensor 108(a) andinjector module confirmatory flow sensor 108(b).

At step 440, therapeutic gas delivery system 100 can prompt users toattach the gas sampling downstream from the injector module, asillustrated in FIG. 5 . For example, a user may be instructed to attacha sample-T to the outlet of injector module 107, where the sample-T maydivert at least a portion of the gas exiting injector module 107 to thegas sampling subsystem 180. The sample-T may be downstream from injectormodule 107 flow sensor(s) 108(a), 108(b).

At step 442, in various embodiments, flow of the therapeutic gas throughone or more of flow control channels 141(a), 141(b), 161 may purge airout of delivery tube 111, injector module 107, and/or any conduitsupstream from and/or in fluid communication with delivery tube 111and/or injector module 107. For example, therapeutic gas delivery system100 may purge delivery tube 111, injector module 107, and/or anyconduits upstream from and/or in fluid communication with delivery tube111 and/or injector module 107 by providing therapeutic gas from flowcontrol channel 141(a) and/or any other flow control channel. Inexemplary embodiments, during purges the gas analyzer may reference roomair (e.g., mitigate exposure to high concentration NO, performcalibration, etc.).

At step 444, therapeutic gas delivery system 100 can confirm if thepurge, at step 442, was successful by detecting the purge with any ofthe flow sensors in fluid communication with the conduit where the purgeflowed therapeutic gas through and/or by taking a sample of the purgeflow, via the sample T connected to the injector module, using the gasanalyzing subsystem 180. If not successful then therapeutic gas deliverysystem 100 can proceed to failure processes, at step 406.

At step 446, in exemplary embodiments, therapeutic gas delivery system100 can perform verification processes of any and/or all flow sensorsaffiliated with first gas supply subsystem 110(a), a second gas supplysubsystem 110(b), a primary gas delivery subsystem 140, a secondary gasdelivery subsystem 160, and/or a gas analyzing subsystem 180. By way ofexample, referring to FIG. 6 , one or more embodiments of the presentinvention provide an exemplary processes (e.g., triangulation of failurethat can be used for pre-use performance verification, triangulation offailure that can be used for performance verification during delivery oftherapeutic gas, etc.) for determining whether various sensors areproperly calibrated by cross-checking with other sensors.

At step 602, the therapeutic gas delivery system 100 delivers aratio-metric flow of therapeutic gas according to a dose set by the useror according to a predetermined dose that is part of the pre-useperformance verification procedure. Of course, similar techniques can beused for performance verification during delivery of therapeutic gas.The ratio-metric flow can be provided by the components in fluidcommunication with first primary flow control channel 141(a) (e.g. firstprimary control valve 143(a), first primary delivery flow sensor 146(a)and first primary confirmatory flow sensor 148(a)), the components influid communication with second primary flow control channel 141(b)(e.g. second primary control valve 143(b), second primary delivery flowsensor 146(b) and second primary confirmatory flow sensor 148(b)), thecomponents in fluid communication with secondary flow control channel161(a) (e.g. secondary flow control valve 163, secondary delivery flowsensor 166, and secondary confirmatory flow sensor 168)), etc. In one ormore embodiments, components associated with one flow control channel isoperated and verified, followed by operation and verification of asecond set of components, followed by operation and verification of athird set of components, etc., until all relevant components have beenverified.

At step 604, the primary delivery subsystem controller 144 and/orsecondary gas delivery subsystem controller 164 compares the NOconcentration measured by gas sensor 182 to the ratio-metricconcentration calculated using the therapeutic gas flow reported by thedelivery flow sensor 146(a), 146(b), 166, the NO concentration in thegas cylinder, the breathing gas flow reported by injector moduledelivery flow sensor 108(a), and/or flow sensor 174, 176. By way ofexample, the ratio-metric concentration for a given set of sensors iscalculated as follows:

YNOcalc=(QNOmeasYNOcyl)/(QNOmeas+Qi)

Where

YNOcalc=calculated ratio-metric NO concentration (ppm)

QNOmeas=measured NO flow rate (SLPM)

YNOcyl=NO cylinder concentration (ppm)

Q.sub.i=injector module flow rate (SLPM)

In the above equation, QNOmeas can be provided by first primary deliveryflow sensor 146(a), second primary delivery flow sensor 146(b), firstprimary confirmatory flow sensor 148(a), second primary confirmatoryflow sensor 148(b), secondary delivery flow sensor 166 or secondaryconfirmatory flow sensor 168, and Q.sub.i can be provided by injectormodule delivery flow sensor 108(a), injector module confirmatory flowsensor 108(b), flow sensor 174 or flow sensor 176, depending on whichflow sensors are being verified.

If the calculated ratio-metric concentration does not match the NOconcentration measured by gas sensor 182, then the flow information fromdelivery flow sensor 146(a), 146(b), 166 is compared to the flowinformation from its respective confirmatory sensor 148(a), 148(b), 168at step 606. If the flow information from delivery flow sensor 146(a),146(b), 166 does not match the flow information from confirmatory sensor148(a), 148(b), 168, then step 608 provides that the user can beinstructed to service the components in fluid communication with theflow control channel being verified, which includes the delivery flowsensor 146(a), 146(b), 166, the respective confirmatory sensor 148(a),148(b), 168 and/or respective the control valve 143(a), 143(b), 163.Furthermore, if during therapy, the device can fail over to an alternateflow control channel or secondary delivery subsystem. If the flowinformation from delivery flow sensor 146(a), 146(b), 166 matches theflow information from confirmatory sensor 148(a), 148(b), 168, then theflow information from injector module delivery flow sensor 108(a) orflow sensor 174 is compared to the flow information from injector moduleconfirmatory flow sensor 108(b) or flow sensor 176 at step 610. If theflow information injector module delivery flow sensor 108(a) or flowsensor 174 does not match the flow information from injector moduleconfirmatory flow sensor 108(b) or flow sensor 176, then step 612provides that the user can be instructed to replace the injector module107. Furthermore, if during therapy, in one or more embodiments thedevice can use confirmatory flow sensor 108(b) for flow control and/ordelivery. If the flow information from injector module delivery flowsensor 108(a) or flow sensor 174 matches the flow information frominjector module confirmatory flow sensor 108(b) or flow sensor 176, thenstep 614 provides that the user can be instructed to service (e.g.calibrate, replace) gas sensor 182 and/or the device can display theratio-metric calculated concentrations to the user.

If the calculated ratio-metric concentration matches the NOconcentration measured by gas sensor 182, then the primary deliverysubsystem controller 144 and/or secondary gas delivery subsystemcontroller 164 compares the NO concentration measured by gas sensor 182to the ratio-metric concentration calculated using the therapeutic gasflow reported by the confirmatory sensor 148(a), 148(b), 168, the NOconcentration in the gas cylinder, and the breathing gas flow reportedby injector module confirmatory flow sensor 108(b) or flow sensor 176 atstep 616.

If the calculated ratio-metric concentration for the confirmatorysensors does not match the NO concentration measured by gas sensor 182,then the flow information from delivery flow sensor 146(a), 146(b), 166is compared to the flow information from its respective confirmatorysensor 148(a), 148(b), 168 at step 606. If the flow information fromdelivery flow sensor 146(a), 146(b), 166 does not match the flowinformation from confirmatory sensor 148(a), 148(b), 168, then step 608provides that the user can be instructed to service the components influid communication with the flow control channel being verified, whichincludes the delivery flow sensor 146(a), 146(b), 166, the respectiveconfirmatory sensor 148(a), 148(b), 168 and/or respective the controlvalve 143(a), 143(b), 163. Furthermore, if during therapy, the devicecan fail over to an alternate flow control channel or secondary deliverysubsystem. If the flow information from delivery flow sensor 146(a),146(b), 166 matches the flow information from confirmatory sensor148(a), 148(b), 168, then the flow information from injector moduledelivery flow sensor 108(a) or flow sensor 174 is compared to the flowinformation from injector module confirmatory flow sensor 108(b) or flowsensor 176 at step 610. If the flow information from injector moduledelivery flow sensor 108(a) or flow sensor 174 does not match the flowinformation from injector module confirmatory flow sensor 108(b) or flowsensor 176, then step 612 provides that the user can be instructed toreplace the injector module 107. Furthermore, if during therapy, in oneor more embodiments the device can use confirmatory flow sensor 108(b)for flow control and/or delivery. If the flow information from injectormodule delivery flow sensor 108(a) or flow sensor 174 matches the flowinformation from injector module confirmatory flow sensor 108(b) or flowsensor 176, then step 614 provides that the user can be instructed toservice (e.g. calibrate, replace) gas sensor 182 and/or the device candisplay the ratio-metric calculated concentrations to the user.

If the calculated ratio-metric concentration for the confirmatorysensors matches the NO concentration measured by gas sensor 182, thenthe components in fluid communication with the flow control channel aresuccessfully verified as provided at step 618. The components in fluidcommunication with the other flow control channels can then be verifiedby starting at step 602. Once all relevant components have beenverified, then the performance verification can proceed further asprovided by FIGS. 4A-4C.

Referring back to FIGS. 4A-4C, at step 448, if any and/or allperformance verification processes, at step 446, were not successfulthen therapeutic gas delivery system 100 can proceed to failureprocesses, at step 406. If successful then performance verificationprocesses can verify three-way 171, at step 450.

Therapeutic gas delivery system 100 can verify flow regulating valve170, which may be a three-way valve 170 by actuating it such that aninitial flow rate (e.g., zero flow) is delivered to the injector module;actuating valve 170 so another set flow rate (e.g. 1 SLPM) is deliveredto the injector module; detecting the change seen at the injector moduleusing injector module delivery flow sensor 108(a) and/or injector moduleconfirmatory flow sensor 108(b); and/or then actuating three way valve170 such that the initial flow rate (e.g., zero flow) returns.

By way of example, therapeutic gas delivery system 100 can verifythree-way valve 170 by actuating the three way valve to deliver lowpressure air/O2 at an initial flow rate (e.g., wall flow 10 SLPM); thenactuating three way valve 170 to deliver therapeutic gas throughsecondary delivery subsystem 160, via flow control channel 161, atsecondary delivery flow rate (e.g. 1 SLPM); detecting the incrementalchange seen at the injector module using injector module delivery flowsensor 108(a) and/or injector module confirmatory flow sensor 108(b)(e.g., flow increase of about 10%); and/or then actuating three wayvalve 170 such that the therapeutic gas flow, NO, flows to 111, and isdelivered downstream to the injector module flow sensors and the initialflow rate (wall flow 10 SLPM) returns (e.g., as the incremental NO flowis no longer measured by the injector module flow sensors). In at leastsome instances, during verification of three-way valve 170, the gasanalyzer may be exposed to room air, for example, to preventover-saturation of NO sensor (e.g., from 4880 ppm high concentration).

At step 452, if any and/or all performance verification processes, atstep 450, were not successful then therapeutic gas delivery system 100can proceed to failure processes, at step 406. If successful thenperformance verification processes prompt the user to connect theinjector module and/or sample T to the patient breathing circuit (e.g.,as depicted in FIGS. 1-3 ) and/or connect the external manualventilation device (e.g., bag valve mask) to outlet 170, at step 454.

At step 456, therapeutic gas delivery system 100 can verify injectormodule 107 is facing the correct direction and/or in the correctposition in the breathing circuit.

In exemplary embodiments, therapeutic gas delivery system 100 candetermine when injector module 107 has been inserted into a breathingcircuit 209 backwards. This can be accomplished because, amongst otherthings, the injector module delivery flow sensor and/or the injectormodule confirmatory flow sensor can be bi-directional flow sensorsconfigured to determine the direction of gas flow through the injectormodule 107. In various embodiments, the injector module delivery flowsensor and the injector module confirmatory flow sensor are arranged inlocated relative to each other in series, parallel, skewed, and/or anyother configuration.

In various embodiments, the system may guide a user through system setupat the bedside (e.g., at the bedside of a patient and/or intendedpatient, etc.), which may comprise providing instructions on secondarydelivery subsystem connections (e.g. attachment of a valve-maskassembly), injector module 107 connections into the breathing circuitand verify the correct orientation, humidity/temp levels, etc, and onsample T placement in the breathing circuit. In various embodiments, thebi-directional flow sensors in the injector module may indicate gas flowdirection and verify the correct orientation to the user.

If injector module 197 is oriented such that it is not facing thecorrect direction, system 100 may prompt the user to re-positioninjector module 107 such that it is facing the correct direction.

At step 458, if the injector module is positioned properly in thebreathing circuit, therapeutic gas system 100 can then be ready for use(e.g., ready to delivery therapeutic gas to a patient).

In exemplary embodiments, at any time during use of therapeutic gasdelivery system 100, the gas analyzer and/or system 100 can initiate alow calibration, at step 470, as described above. For ease, step 470 isshown as occurring after step 404. This is merely for ease and is in noway meant to be a limitation. At step 472, if the low calibration is notsuccessful then therapeutic gas delivery system 100 can retry the lowcalibration and/or proceed to failure processes, at step 406. If the lowcalibration is successful it then the sensor is calibrated and may beused during delivery of therapeutic gas to a patient and/or during anyrelevant steps in the pre-use verification processes (e.g., step 442,etc.).

In exemplary embodiments, at any time during use of therapeutic gasdelivery system 100, system 100 can initiate a manifold leak test, atstep 480, as described above. At step 482, if the manifold leak test isnot successful then therapeutic gas delivery system 100 can proceed tofailure processes, at step 406. If the manifold leak test is successfulit then the manifold may be used during delivery of therapeutic gas to apatient and/or during any relevant steps in the pre-use verificationprocesses (e.g., step 454, etc.).

Although the invention herein has been described with reference toparticular embodiments, it is to be understood that these embodimentsare merely illustrative of the principles and applications of thepresent invention. It will be apparent to those skilled in the art thatvarious modifications and variations can be made to the method andapparatus of the present invention without departing from the spirit andscope of the invention. Thus, it is intended that the present inventioninclude modifications and variations that are within the scope of theappended claims and their equivalents.

It is to be understood that the invention is not limited to the detailsof construction or process steps set forth in the above description. Theinvention is capable of other embodiments and of being practiced orbeing carried out in various ways.

Reference throughout this specification to “one embodiment,” “certainembodiments,” “one or more embodiments” or “an embodiment” means that aparticular feature, structure, material, or characteristic described inconnection with the embodiment is included in at least one embodiment ofthe invention. Thus, the appearances of the phrases such as “in one ormore embodiments,” “in certain embodiments,” “in one embodiment” or “inan embodiment” in various places throughout this specification are notnecessarily referring to the same embodiment of the invention.Furthermore, the particular features, structures, materials, orcharacteristics may be combined in any suitable manner in one or moreembodiments.

What is claimed is:
 1. A method of providing therapeutic gas from asecondary delivery subsystem, comprising: detecting a problem with aprimary gas delivery system configured to deliver a therapeutic gasflow; automatically switching therapeutic gas flow control to a flowcontrol channel of the secondary delivery subsystem, wherein the flowcontrol channel is operable to receive the therapeutic gas flow and isin fluid communication with a secondary shut off valve, a secondary flowcontrol valve, a secondary delivery flow sensor, and a secondaryconfirmatory flow sensor; and switching a flow regulating valve todeliver the therapeutic gas to a primary outlet, a low pressure outlet,and an injector module, wherein the flow regulating valve is at ablending junction and is in fluid communication with the flow controlchannel.
 2. The method of claim 1, further comprising: receiving a setdose of therapeutic gas from a primary gas delivery subsystem of theprimary gas delivery system; receiving a flow value from the secondarydelivery flow sensor and/or a secondary confirmatory flow sensor;calculating a flow rate of the therapeutic gas through the low pressuredelivery flow sensor or the low pressure confirmatory flow sensor toprovide a dose of the therapeutic gas exiting the blending junction; andcomparing the dose of the therapeutic gas exiting the blending junctionto the set dose.
 3. The method of claim 2, wherein the calculated doseof therapeutic gas is calculated using a known concentration of thetherapeutic gas from a therapeutic gas source, the amount of lowpressure oxygen and/or air using information from the secondary deliveryflow sensor and/or the secondary confirmatory flow sensor, and theamount of therapeutic gas flow from flow control channel going to theblending junction using information from the secondary delivery flowsensor and/or the secondary confirmatory flow sensor.
 4. The method ofclaim 1, wherein the problem detected is loss of communication with theprimary gas delivery system, a failure in one or more of the flowcontrol channels of primary gas delivery system, failure at a gasanalyzer of the primary gas delivery system, or power failure of theprimary gas delivery system.
 5. The method of claim 4, wherein thesecondary delivery subsystem has its own internal battery backupseparate from a main system battery.
 6. The method of claim 1, furthercomprising: performing ratio-metric calculations for a concentration oftherapeutic gas being delivered based on flow values from the secondarydelivery flow sensor and/or the secondary confirmatory flow sensor, andfrom an injector module delivery flow sensor and/or an injector moduleconfirmatory flow sensor.
 7. The method of claim 6, wherein thesecondary delivery flow sensor and/or the secondary confirmatory flowsensor provides monitoring of the secondary delivery subsystem thatcomprises 3 sets of sensors for triangulation of failure, including theinjector module delivery flow sensor and/or the injector moduleconfirmatory flow sensor, the secondary delivery flow sensor and/or thesecondary confirmatory flow sensor, and the therapeutic gas sensor. 8.The method of claim 7, further comprising: comparing flow rate valuesfrom the injector module delivery flow sensor and/or the injector moduleconfirmatory flow sensor, the secondary delivery flow sensor and/or thesecondary confirmatory flow sensor, and the therapeutic gas sensor;comparing the ratio-metric concentration of therapeutic gas to a setconcentration of therapeutic gas; and determining if any components ofthe primary gas delivery subsystem or the secondary gas deliverysubsystem have failed based on the comparisons.
 9. The method of claim1, further comprising generating an alert to a user if a problem isdetected.
 10. The method of claim 9, further comprising generating analarm signal if flow values from the low pressure confirmatory flowsensor the low pressure delivery flow sensor are not about the same. 11.The method of claim 1, further comprising communicating pressure valuesfrom the pressure sensor to the secondary delivery subsystem controller,and detecting pressure fluctuations in the pressure sensor.
 12. Themethod of claim 11, further comprising opening an overpressure valve influid communication with the primary outlet at a predetermined pressureto avoid pressure surges.
 13. The method of claim 1, wherein the lowpressure outlet is operable for connection to a manual ventilationdevice.
 14. The method of claim 1, wherein the primary outlet isconnected to a low pressure inlet port operable for connection to a lowpressure air/O2 supply.